Female Karyotype Research Articles

6611 ACTH deficiency due to TBX19 mutation mimics complete adrenal insufficiency in a newborn

Abstract Disclosure: T. Reinehr: None. P.M. Holterhus: None. S.A. Wudy: None. A. Richter-Unruh: None. C. Spratte: None. C. Roll: None. Isolated ACTH deficiency (IAD) is a rare cause of adrenocortical insufficiency. T-box transcription factor 19 (TBX19) mutations are responsible for more than 60% of neonatal cases of IAD. To the best of our knowledge, we present for the first time a newborn with ACTH deficiency due to a TBX19 mutation with almost steroid-free plasma and urine: At day 2 of life, the female newborn (birth weight 3190g, length 52 cm, 40+1 gestational age) was transferred to our neonatal intensive care unit for severe hypoglycemia (12 mg/dl), which responded to intravenous glucose infusion. Surprisingly, the sodium serum concentrations decreased from 140 mmol/l at day 2 of life to 126 mmol/l at day 7 of life. There were no clinical signs of adrenal insufficiency such as vomiting or hypotonia. Treatment with oral sodium-chloride 5.85% was started. Endocrine diagnostic work-up performed at day 8 of life demonstrated normal values of fT4, HGH and IGFBP-3 ruling out pituitary involvement of these axes, while ACTH serum concentrations were markedly decreased (1.5 pg/ml). Liquid- chromatography-mass spectrometry (LC-MS/MS) revealed nearly absent glucocorticoids (17-hydroxyprogesterone <0.12 nmol/l, 11-deoxycortisol <0.08 nmol/l, cortisol <4.2 nmol/l, and cortisone 1.3 nmol/l (norm value [nv]: 17-138 nmol/l)). Androgens were undetectable (testosterone <0.02 nmol/l, androstenedione <0.08 nmol/l). Mineralocorticoids were severely reduced (11-desoxycorticosterone 0.1 nmol/l (nv: 0.2-1.0 nmol/l), corticosterone 0.6 nmol/l (nv: 1-24 nmol/l), aldosterone 0.1 nmol/l (nv: 0.8-2.3 nmol/l)). In urine spot, gas chromatography-mass spectrometry (GC-MS) demonstrated subnormal excretion of C19 and C21 steroids including fetal zone steroids. Serum and urine measurements were interpreted by the labs as a typical finding similar to StAR defect. The genetic analyses revealed a normal female karyotype (46,XX) and ruled out CYP11A1 and StAR, mutations but demonstrated a homozygous missense mutation in TBX19 (c.172A>G, p.(Thr58Ala)). After 3 months of life under treatment with hydrocortisone (10mg/m² divided in 3 doses) and fludrocortisone (0.05 mg divided in 2 doses), cortisol was normal (320 nmol/l) and DHEAS was undetectable (<3 nmol/l). While androgens were in normal range (testosterone 2.6 nmol/l, androstenedione 0.28 nmol/l), 11-deoxycorticosterone was normal (0.74 nmol/l), corticosterone was undetectable (<0.5 nmol/l) and aldosterone was decreased (0.12 nmol/l nv: 0.8-1.2 nmol/l). At this time point, ACTH was <4 pg/ml, renin 1.6 mIU/l, LH 0.7 mIU/l and FSH 24.5 mIU/ml. This case demonstrated that isolated ACTH deficiency should be considered as a potential differential diagnosis in complete adrenal steroid insufficiency in newborns. Our data suggest that ACTH is not only necessary for cortisol biosynthesis but also for sufficient mineralocorticoid and androgen production by the adrenals in neonates. Presentation: 6/3/2024

Comprehensive management of Mayer-Rokitansky-Küster-Hauser syndrome management: A case report.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also known as Müllerian aplasia, is a congenital condition characterized by uterine and upper vaginal aplasia. It affects females with a normal female karyotype and typical secondary sex characteristics. The aim of this case report was to highlight the multidisciplinary management approach for MRKH syndrome, focusing on tailored interventions to address physical and psychological challenges and improve reproductive prospects. A 26-year-old married female presented to Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi, Wardha, India, in January 2023 with primary amenorrhea. Physical examination revealed a blind vagina and a hypoplastic uterus, indicative of MRKH syndrome. Further evaluation, including pelvic magnetic resonance imaging (MRI), confirmed Müllerian duct abnormalities and bilateral ovarian anomalies. The absence of a functional vagina significantly impacted the patient's quality of life, leading to difficulties with sexual intercourse and emotional distress related to infertility. A collaborative approach involving a gynecologist and a psychiatrist at AVBRH was initiated to address these challenges. The patient underwent vaginoplasty to create a neovagina, enhancing the sexual function and intimate relationship with the spouse. However, due to the hypoplastic uterus, achieving motherhood through traditional means was not possible. Therefore, assisted reproductive techniques, in particular surrogacy, were explored. Normal, functional ovaries were harvested from the patient for use in surrogacy procedures. This comprehensive management strategy exemplifies the challenges associated with MRKH syndrome and underscores the importance of tailored interventions and long-term follow-up. The case highlights the significance of collaborative care in improving the quality of life and reproductive prospects for individuals with MRKH syndrome.

The significance of follow-up in patients with dysmorphic features: a case from clinical practice

Background. Kabuki syndrome is a rare disorder, that is characterized by typical facial dysmorphism, hypotonia, delay in intellectual and motor development. Case report. We present a case of a girl in whom polycystic left kidney was prenatally established. Born prematurely in 37 weeks by C section due to oligohydramnios. After birth, atresia of the anus with fistula, cysts in the left and reduced dimensions of the right kidney, were further established. A normal female karyotype was found and targeted sequencing analysis was conducted on a panel of 81 genes associated with renal abnormalities – no pathogenic variants were detected. The child was then followed up by its general practitioner. At the age of 2 years, she was again referred for genetic counseling, which revealed the following dysmorphic signs – long eye palpebral fissuras with ectropion of the lower eyelid, sparsed lateral eyebrows, depression of the nasal bridge, brachydactyly and others characteristic of Kabuki’s syndrome. The conducted molecular genetic analysis confirmed the clinical diagnosis – a likely pathogenic variant in the KMT2D gene was established. Conclusions. Certain pathognomonic facial may not present at birth and only appear after a few years. Therefore, monitoring of the evolution of dysmorphic traits is required.

Karyotype Symmetry/Asymmetry Index (S/AI) in Bovidae Taxa

The chromosomal data, particularly karyotype asymmetry, provide valuable information on karyotypic phylogeny and speciation. The karyotype asymmetry is a good expression of the general morphology of chromosomes. The S/AI is a formula used to calculate the karyotype asymmetry. The formula was applied to 79 species and five subspecies from 46 genera for female individuals and 72 species and five subspecies from 42 genera for male individuals in the Bovidae family. According to the S/AI values between 1.2903 and 3.0000, the dendrograms were drawn to demonstrate the interspecies relationships in the family. The karyotypes of females were symmetrical in 10 species and two subspecies from 6 genera and between symmetrical and asymmetrical in 69 species and three subspecies from 40 genera. Male karyotypes were symmetrical in 10 species and two subspecies from 6 genera and between symmetrical and asymmetrical in 62 species and three subspecies from 36 genera. The dendrograms will contribute to phylogenetic studies in mammals. Already, they showed results similar to those of molecular taxonomy.

Noninvasive prenatal screening in a pregnant woman with a history of stem cell transplant from a male donor: A case report and literature review.

As a screening method, inaccuracies in noninvasive prenatal screening (NIPS) exist, which are often attributable to biological factors. One such factor is the history of transplantation. However, there are still limited reports on such NIPS cases. We report an NIPS case of a pregnant woman who had received a stem cell transplant from a male donor. To determine the karyotype in the woman's original cell, we performed chromosome microarray analysis (CMA) on her postnatal blood and oral mucosa. To comprehensively estimate the cell-free DNA (cfDNA) composition, we further performed standard NIPS procedures on the postnatal plasma. Moreover, we reviewed all published relevant NIPS case reports about pregnant women with transplantation history. NIPS showed a low-risk result for common trisomies with a fetal fraction of 65.80%. CMA on maternal white blood cells showed a nonmosaic male karyotype, while the oral mucosa showed a nonmosaic female karyotype. The proportion of donor's cfDNA in postnatal plasma was 94.73% based on the Y-chromosome reads ratio. The composition of cfDNA in maternal plasma was estimated as follows: prenatally, 13.60% maternal, 65.80% donor, and 20.60% fetal/placental, whereas postnatally, 5.27% maternal and 94.73% donor. This study expanded our understanding of the influence of stem cell transplantation on NIPS, allowing us to optimize NIPS management for these women.

P967 Allogeneic bone marrow-derived mesenchymal stromal cell therapy for complex perianal and rectovaginal fistulas in Crohn´s disease: a retrospective single-centre study

Abstract Background Perianal fistulising Crohn´s disease (CD) is associated with a high burden of disease and treatment of fistulas remains challenging. Promising data on short-term efficacy of bone marrow-derived mesenchymal stromal cell (bmMSC) treatment emerged in the recent past, but there is limited data regarding long-term efficacy and safety. Methods Between February 2013 and January 2016, patients with non-active CD (Harvey-Bradshaw Index < 5) and draining complex, treatment-refractory perianal or rectovaginal fistulas underwent local bmMSC therapy as compassionate use. After curettage of the fistula tract, patients received three local bmMSC injections biweekly with 20 million cells each. In case of incomplete clinical and radiological healing 3 to 12 months after the first treatment, up to six additional injections with 40 million cells each were administrated, resulting in a maximal cumulative dose of 300 million bmMSC (table 1). We retrospectively analysed patient records for disease course and documentation of adverse events. Clinical remission was defined by closure of external fistula openings without discharge at digital pressure. The modified Van Assche index was assessed before bmMSC treatment as well as in short- and long-term MRI follow-up. Results Six female patients (median age 35 years, range 19 – 46 years) with two or three complex fistulas each were included. In total, 13 fistulas (9 transsphincteric, 2 extrasphincteric and 2 rectovaginal) underwent local bmMSC application (table 1). Median radiological and clinical follow up was 80 months (range, 44 – 98 months) after first local bmMSC injection. 8 of 13 fistulas (62%) exhibited complete closure at last observation. For rectovaginal fistulas, long-term remission was 50 % (1 of 2). Excluding rectovaginal fistulas, 4 of 6 patients (67%) showed long-term closure of all other fistulas. Pelvic MRI showed a decrease in modified Van Assche index from baseline (median score 7.8, range 6.2-9.7) to long-term follow up (median score 2.1, range 1.5-11.7). No immediate adverse events related to bmMSC injections were observed. One patient (p1) was diagnosed with a local adenocarcinoma of the rectum (pT1, pN0, R0) 106 months after first bmMSC injection. MRI control 11 months prior showed complete fistula remission. The tumor exhibited a female karyotype, while bmMSC had been derived from a male volunteer. Conclusion More than 60% of all treatment-refractory CD perianal fistulas showed long-term remission up to 8 years after local allogenic bmMSC therapy.

Cytogenetics and Molecular Diagnosis in Horse Infertility

As the popularity of horse breeding stays steady, many breeders and owners send their horses samples to cytogenetics analysis for signs of infertility or other genetic abnormalities. Here, we report three cases of horses that were subjected to chromosome analysis due to infertility issues. Unfortunately, in the case of the H304 mare, the horse has a normal 64, XX female karyotype and no chromosomal abnormality was observed to explain the infertile issue. In the case of the H305 mare, the horse has a 64, XY male karyotype which indicates genetically male and no sign of chromosomal abnormality under cytogenetic analysis. However, PCR analysis indicates the loss of the SRY in the Y chromosome. This is a typical male to female sex reversal and one of the most common genetic sex abnormalities in horses. In the H306 mare, the horse has only one X chromosome; 63, XO, called X monosomy. This is the most common sex chromosomal abnormality in horses. The combination of clinical cytogenetic analysis and the use of PCR are the strongest tool to determine the chromosomal abnormality in the equine industry and the case H305 is a good example to support how these two different approaches compensate each other to generate a reliable diagnosis. Determination of genetic abnormalities using two techniques will help horse breeders and equine practitioners to make the most informed decisions about breeding plans.

Successful Management of D816V Mutated c-KIT Systemic Mastocytosis with Chronic Imatinib: A Case Report

First characterized in France in 1936, systemic mastocytosis (SM) is a rare disorder by an excessive proliferation and accumulation of abnormal mast cells in extracutaneous tissues (Nettleship et al., 1869). The release of large quantities of vasoactive mediators by these cells results in allergic- and anaphylactic-type reactions in one or more organ systems. Given the similarity of symptoms between allergic reactions and SM and the rarity of the condition, SM is often missed and misdiagnosed (Schwaab et al., 2020). Once considered a subtype of myeloproliferative neoplasms, mastocytosis was reclassified in the 2016 revision to the World Health Organization (WHO) due to advances in understanding of the disorder (Arber, et al., 2016). Presented below is a case of a severe systemic mastocytosis with an initially positive D816V mutated c-kit successfully managed with long-term imatinib use alongside intermittent bone marrow biopsies (BMB) to monitor what is now an indolent systemic mastocytosis. 69 year-old female with a past medical history of paroxysmal atrial fibrilation, hashimoto's thyroiditis, metabolic syndrome, and gastro-esophageal reflux (GERD) presents to clinic for routine management of what was previously severe systemic mastocytosis (SSM) and now is indolent systemic mastocytosis with the help of imatinib. To help control her ISM her medications include a daily histamine-1 blocker (ranitidine), a daily histamine-2 blocker (diphenhydramine), and a twice-daily histamine-1 antagonist (cetirizine). Originally evaluated in 2005 with a bone marrow biopsy (BMB) and found to have a Asp816Val (D816V) c-kit mutation, she was placed on imatinib with significant clinical improvement. This seemed to support that the D816V mutation may cause constitutional activation of the c-kit transmembrane protein and thus sensitivity to imatinib therapy. This despite the FDA labeling for imatinib as only to be used in SM patients without the common D816V mutation or for whom the mutational status is unknown (Reference ID: 4957210, 2001). Interestingly, after being placed on imatinib her repeat bone marrow biopsies in 2011 and 2015 indicated that the D816V mutation was no longer present in her CD117 positive mast cells but continued to benefit from imatinib therapy. This finding is suggestive of two unique mast cell populations as imatinib continued to help maintain a low tryptase level and decrease the severity of reactions. When reactions did occur, she treated them at one point with a cocktail of an histamine-2 blocker (ranitidine), histamine-1 blocker (diphenhydramine), and a mast cell stabilizer (cromolyn) and without requiring the use of epinephrine. As a part of her longitudinal observation, she received an additional BMB in 2022 that revealed a minimal residual monocytosis that persisted with less than 10% nucleated cells, an age-appropriate trilinear hematopoiesis, decreased iron stores without ringed sideroblast formation. Flow cytometry was indicative of a typical female karyotype with the population of aberrant mast cells that is consistent with the diagnosis of ISM. Importantly, no abnormalities were detected in the FLT3, IDH1, IDH2, NPM1 genes which, if abnormal, could obfuscate the apparent efficacy of imatinib treatment in the management of SM. Given the dearth of mastocytosis in the BMB and the absence of ongoing end-organ damage, the patient meets the definition of ISM. After the most recent BMB the patient altered her daily regimen due to gastric upset and found she could take of her histamine-1 blocker (diphenhydramine) once daily along with a twice daily regimen of her imatinib (split into two smaller daily doses), histamine-1 antagonist (cetirizine), her histamine-2 antagonist (famotidine), and citalopram (selective serotonin reuptake inhibitor or SSRI) with improved symptomatic control to this day. This case serves to illustrate the diagnostic and therapeutic challenges associated with SM, as well as the potential therapeutic use of imatinib in patients with D816V outside of its original FDA indication. Further characterization of the effect of imatinib on D816V mutated SM may warrant the consideration of expanding the FDA indications for imatinib as its role and efficacy outside of solely D816V negative c-kit MS.

Congenital dysfunction of the adrenal cortex on the background of 11β-hydroxylase deficiency

Congenital adrenal dysfunction (CHD) is a variant of hereditary fermentopathies that lead to a violation of the synthesis of cortisol in the adrenal cortex. Late diagnosis of this pathology significantly impairs the quality of life of patients, and in some cases can lead to fatal consequences. The most common form of CHD, occurring in more than 90% of cases, is due to a deficiency of 21-hydroxylase, which is responsible for the synthesis of deoxycorticosterone and 11-deoxycortisol. The prevalence of this form is 1:10,000 to 1:20,000 newborns in the world, in Russia — 1:9500. In second place is the deficiency of 11β-hydroxylase (hypertonic form of HCHD), which affects the synthesis of cortisol. This form of the disease occurs in about 1:100,000 newborns in the world, and in Russia the prevalence of this form is unknown [1].The cause of any form of CHD is mutations in the genes responsible for the synthesis of enzymes or transport proteins involved in the synthesis of cortisol. 11β-hydroxylase is synthesized in the zona fasciculata of the adrenal cortex and is regulated by adrenocorticotropic hormone by a negative feedback mechanism. 11β-hydroxylase deficiency (hypertonic form of HCHD) develops as a result of mutations in the CYP11B gene located on chromosome 8. This mutation blocks the enzymatic conversion of 11-deoxycortisol to cortisol, as well as deoxycorticosterone (DOC) to corticosterone, leading to the accumulation of DOC, which has mineralocorticoid activity. It is the excess of deoxycorticosterone that causes an increase.In 21-hydroxylase deficiency, the clinical picture is primary adrenal insufficiency (deficiency of glucoand mineralocorticoids). The clinical picture of mineralocorticoid deficiency includes salt loss syndrome: arterial hypotension, tachycardia, adynamia, fibrillary muscle twitching, dryness and decreased skin turgor, cyanosis and marbling of the skin. Glucocorticoid deficiency is manifested by muscle weakness, fatigue, hyperpigmentation of the skin. With a deficiency of 11β-hydroxylase, due to an increase in the level of deoxycorticosterone, there is no deficiency of mineralocorticoid activity, on the contrary, against the background of clinical signs of glucocorticoid insufficiency, an increase in blood pressure may be observed. Hyperandrogenism is characteristic of both forms of CHD. Symptoms of hyperandrogenism in females: virilization of the external genitalia, amenorrhea, severe alopecia and hirsutism. In undiagnosed cases of CHD, patients with a female karyotype have a male phenotype.

FRI556 Thyroid Autoimmunity Leading To Premature Ovarian Insufficiency (POI) In A Euthyroid Young Woman

Abstract Disclosure: P. rimal: None. M. Moeed: None. C. Musurakis: None. A. Ojha: None. W. Akhtar: None. C.P. Barsano: None. M.F. Siddiqui: None. Introduction: Premature Ovarian Insufficiency is rare in young women and affects only 0.1% before the age of 30. The causes of POI in most cases remain unidentified, with autoimmunity being responsible for 4-30% of the cases. We present the case of a young euthyroid woman who presented for the evaluation of primary amenorrhea and diagnosed with POI associated with thyroid autoimmunity. Clinical Case: A 28-year-old Afghani woman with no known co-morbidities was referred to endocrinology clinic for the work up of primary amenorrhea. She was a goitrous and had normal secondary sexual characteristics and a history of withdrawal bleeding with OCP. There was no known personal or family history of autoimmune disease. Work up revealed hypergonadotropic hypogonadism with high FSH, 55 mIU/ml[Ref range for postmenopausal woman 16.7-113], high LH, 20.28 mIU/ml [Ref range for postmenopausal woman 10.8-58.69] and low estradiol, <2 pg/ml. Anti-Mullerian hormone was low, <0.08ng/ml [RefRange 0.69-13.39] signifying inadequate ovarian reserves and pelvic ultrasound confirmed atrophic ovaries. Etiological work up revealed normal female karyotype, 46XX, and negative FMR gene mutation testing for Fragile X syndrome. Thyroid functions were normal TSH, 3.3 mIU/L (0.27-4.2) and Free T4, 1.29 ng/dl[Ref Range 0.70-2.7]. Autoimmune work up was negative for adrenal 21-OH antibody and anti-ovarian antibodies. However, patient had strongly positive thyroid peroxidase (TPO) antibodies, 613.77 mIU/L[Ref range 0.0-9.0] consistent with thyroid autoimmunity. DXA scan revealed osteopenia. Thus, the diagnosis of POI associated with thyroid autoimmunity was established. HRT with estradiol patch and progesterone was initiated. Calcium, Vitamin D supplements and fertility counseling were provided. Conclusion: Thyroid disease is the most common autoimmune disease associated with POI. Studies have shown higher risk of POI and infertility in patients with Hashimoto’s and Graves’ diseases with co-existing high titers of TPO or anti-thyroglobulin antibodies. Ovaries are subject to autoimmune attack that leads to diminished ovarian reserves. However, until now the association of isolated elevation of TPO antibodies with POI has not been established. A Study by Osuka et al. did not find any significant difference in AMH levels between TPO and non-TPO positive euthyroid women and concluded that unlike hypothyroid women, thyroid autoantibodies were not likely to influence ovarian reserves in euthyroid women. Our case is unique where POI is associated with isolated elevation of TPO antibodies in the absence of clinical thyroid disease. This signifies the possibility that ovarian failure may precede the onset of thyroid disease in patients with thyroid autoimmunity and should be suspected and treated at an early stage, before ovarian reserves are diminished. Presentation: Friday, June 16, 2023

Generation of an induced pluripotent stem cell line (IGGi002A) from nasal cells of a cystic fibrosis patient homozygous for the G542X-CFTR mutation

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel defective in cystic fibrosis (CF). Several CFTR mutations are causative of CF, among which G542X is a nonsense mutation introducing a premature stop codon which prevents CFTR protein synthesis. We generated a new iPSC line from nasal cells carrying G542X homozygous mutation for CFTR: IGGi002A. This cell line has normal female karyotype, express pluripotency markers and could differentiate into three germ layers in vitro. This iPSC line may be used for disease modeling (cell differentiation and organoid formation) and development of personalized treatments by genome editing or pharmacological screening.

Gender pecularity of the material of reproductive losses

Aim. The prognosis of the reproductive function of women with pregnancy loss is complex and partly based on the results of karyotyping of material of reproductive loss. According to the literature, during conception are formed the same number of male and female fetuses, but more boys are born. The purpose of this study was to evaluate the gender ratio and incidence of chromosomal anomalies in the products of conception (POC). Methods. Banding cytogenetic and interphase mFISH with the centromeric probe panel for chromosomes 13, 14, 15, 16, 17, 18, 21, 22, X and Y were used. Results. Were examined 497 cases of material POC. Among all samples, female karyotype was established in 273 cases (54.9 %), and male karyotype in 224 cases (45.1 %). Gender ratio of female to male in the POC, regardless of presence or absence of chromosomal anomalies, is 1.22:1. Conclusions. Depending on presence or absence of chromosomal anomalies in POC, the gender ratio differs: with a normal karyotype, female-to-male ratio is 1.09:1, and with an abnormal karyotype, it is 1.6:1, respectively

Morris syndrome (Androgen Insensitivity Syndrome)

Morris syndrome, also known as Androgen Insensitivity Syndrome (AIS), is an intriguing and extraordinary genetic condition that exerts a remarkable influence on individuals with male sex chromosomes (XY). Within the realm of this rare syndrome, the body displays a captivating indifference to androgens, the very essence of male hormones like testosterone, leading to the emergence of physical characteristics typically associated with the female gender. It is an occurrence that befalls a mere fraction of the population, affecting around 1 in 20,000 individuals. Morris syndrome is caused by a genetic mutation located on the sex X chromosome affecting the AR (androgen receptor) gene. Androgen insensitivity syndrome is characterized by the presence of external female phenotype, 46,XY karyotype, and intraabdominal testes. This syndrome is the third most frequent cause of primary amenorrhea, after gonadal dysgenesis and congenital absence of the vagina. In approximately 40% of AIS patients, there is no family history of the disease. Morris syndrome unfolds with an intricate interplay of internal and nonfunctional testicles, which, despite their presence, fail to fulfill their intended biological purpose of sperm production. Meanwhile, on the external front, the genitalia manifest a striking semblance to that of the female anatomy, featuring a vagina and labia. Additionally, some individuals with Morris syndrome may witness the existence of an enlarged clitoris, bearing an uncanny. Comprehending Morris syndrome is vital for healthcare professionals to offer accurate diagnoses and appropriate treatment modalities. Increased awareness among the general populace can foster an inclusive and supportive environment for individuals navigating life with Morris syndrome. Objective: The objective of this article is to provide a comprehensive understanding of Morris syndrome, also known as Androgen Insensitivity Syndrome (AIS), including its genetic basis, clinical manifestations, challenges faced by individuals with the syndrome, and the importance of accurate diagnosis and appropriate treatment modalities. Methods: To achieve the objective, the article will employ a literature review approach, drawing information from scientific and medical sources. Peer-reviewed research articles, medical textbooks, and authoritative online resources will be consulted to gather relevant information on Morris syndrome.

Specifičnost sestrinske skrbi u zbrinjavanju sijamskih blizanaca

Conjoined ("Siamese”) twins are one of the rarest congenital anomalies with an incidence of about 1.47 per 100,000 births in the Western world. This rare natural phenomenon is present in only 1% of monozygotic twins, i.e., 0.05% of live births. Most of them are stillborn (40-60%) or die early in life. The majority of live births are female (75%), which is why the female karyotype is considered to be beneficial in terms of survival. Conjoined twins are created when the zygote begins to separate after 13 days post-fertilization, at a time when the so-called embryonic disc has already been formed. Instead of producing two separate embryos, this late separation causes incomplete separation of the embryos. The name comes from conjoined twin brothers Chang and Eng Bunker, who were born in Siam. Surgical separation of conjoined twins is usually a very demanding and complex procedure, and often not even possible. Survival after separation depends on the type of connection. This paper presents the case of conjoined twins who were born at 33 weeks. At 11 weeks of pregnancy, the doctors suspected that the twins were joined ventrally (omphalopagus – twins joined at the abdomen). The diagnosis was confirmed by fetal MRI at 21 weeks. Separation was indicated at the age of 45 days and a combined body weight of 4,700 g. Long postoperative recovery and treatment lasted three months and was complicated by infections and problems with the healing of the surgical wound of one of the twins. Treatment and recovery required a multidisciplinary approach and a well-educated team of doctors and nurses.

Generation of a FLNA knockout hESC line (WAe009-A-P) to model cardiac valvular dysplasia using CRISPR/Cas9

The FLNA gene encodes the cytoskeletal protein filamin A which plays a key role in the structure and function of the cardiac valves. Truncating FLNA mutations are associated with cardiac valvular dysplasia. To further understand the exact role of FLNA in this disease, we have generated a human FLNA knockout cell line from H9 using CRISPR/Cas9 technology in this study. This cell line WAe009-A-P has a 2 bp deletion in the exon 2 of FLNA gene which resulted in a frameshift in the translation of FLNA and no FLNA protein was detected in this cell line. Moreover, WAe009-A-P also expressed pluripotency markers, had a normal female karyotype (46XX) and maintained the ability to differentiate into the three germ layers in vitro.

Artiodactyla Takımının Familya ve Türlerinin Karyotip Simetri/Asimetri İndeksi (S/AI) ile Karşılaştırılması

The S/AI formula is a parameter used to determine the karyotype asymmetry in higher animals and humans. The formula was performed to the 47 Artiodactyla species. According to the S/AI values between 1.0000 and 3.0000, the dendrograms were drawn demonstrating the interspecies and interfamilies relationships in Artiodactyla. The female karyotype types are between symmetric and asymmetric in the eight families, 18 genera and 36 species; symmetric in the five families, nine genera and 10 species; full symmetric in the only one family, genus and species. The male karyotype types are between symmetric and asymmetric in the 8 families, 18 genera and 34 species; symmetric in the five families, eight genera and nine species; full symmetric in the only one family, genus and species.

P-703 The role of maternal polymorphic karyotype variants among embryonic ploidy and mosaicism status in patients undergoing IVF treatments

Abstract Study question Is there a relationship between the chromosomal status of biopsied embryos and the presence of polymorphic variants in the female karyotype in IVF cycles? Summary answer The chromosomal status of biopsied embryos is prejudiced because of the presence of specific maternal polymorphic variants (qh-, qh+ and ps+) or combinations of them. What is known already Due to the increasing average age of patients who undergo IVF cycles with their own oocytes, more cycles are performed with embryo biopsy for preimplantation genetic test of aneuploidies (PGT-A). Thus, advanced maternal age has been defined as the main factor causing embryonic chromosomal abnormalities. However, few studies have established direct relationships with other factors. The prevalence of chromosomal polymorphic variants has a higher incidence in the infertile population, which is why there is a need to know the role they play in the genetic inheritance of embryos. Study design, size, duration Retrospective evaluation of a cohort of women who underwent autologous IVF cycles and karyotyping. The sample included 162 IVF cycles with embryo biopsy on D5 and/or D6 for PGT-A, performed between July 2017-December 2021: control group (CG) with normal karyotype (86) and study group (SG) with presence of polymorphisms (76). We studied the connection between maternal karyotype polymorphisms and molecular genetic outcomes in terms of euploid, mosaic, and aneuploid blastocyst rates. Participants/materials, setting, methods The analysis of the karyotype of women, prior to the IVF cycle, was performed using the guidelines of the International System for Human Cytogenetic Nomenclature (ISCN). The trophoectoderm biopsies on D5 and/or D6 blastocysts were analysed by NGS using the Illumina platform (VeriSeq Illumina®, San Diego, CA, USA). The association between the different polymorphic variants in the female karyotype and chromosomal status of embryos was analysed using R (v. 4.2.0) statistical software. Main results and the role of chance We analyzed the results of 483 embryos from 162 IVF-PGT-A cycles. Mean female age was 39.05±2.72 (CG) and 38.97±2.90 (SG). Mean number of mature oocytes (MII) was 7.16±3.94 (CG) and 8.01±5.33 (SG). Mean number of biopsied embryos was 2.97±2.15 (CG) and 2.93±1.88 (SG). No statistically significant differences were found between the CG and SG groups in terms of the rate of euploid embryos: 26.99% vs 21.50% (p = 0.3), transferable mosaic embryos: 8.90% vs 6.76% (p = 0.5), aneuploid embryos: 61.98% vs 69.96% (p = 0.12) and non-informative embryos: 2.13% vs 1.78% (p = 0.2), respectively. However, an increase in the rate of chromosomally abnormal embryos was observed when analysing each polymorphism individually. In females carrying the qh+ variant, we found a statistically significant decrease in the euploid embryo rate: 10.97% vs 26.00% found in CG (p = 0.036). Moreover, the variants qh+ and ps+ increased the rate of aneuploid embryos: 84.17% vs 63.48% in CG (p = 0.013) and 73.52% vs 61.30% in CG (p = 0.021), respectively. Furthermore, it is found that the qh- variant increased the rate of transferable mosaic embryos: 20.00% vs 8.90% in CG (p = 0.025). The results were corrected for confounding variables such as maternal age, oocyte origin and male factor variables, including polymorphic variants in the male karyotype. Limitations, reasons for caution Presence of unmeasured variables that may influence the results. Larger prospective studies including homogeneous cohorts are needed in order to corroborate our initial results. Wider implications of the findings The results show that polymorphic variants in the female karyotype may have a direct effect on the embryonic ploidy and mosaicism status. Therefore, it would be advisable for patients who undergo IVF-PGT-A cycles to have a karyotype performed and be informed of the implications that it may entail. Trial registration number Not applicable

P-235 Influence of female karyotype polymorphic variants on oocyte quality and embryo development

Abstract Study question Do polymorphic variants in the karyotype of women undergoing an IVF cycle directly affect oocyte and embryo laboratory parameters? Summary answer The presence of certain polymorphic variants negatively affects the oocyte survival rate and the blastocyst quality in an IVF cycle. What is known already In the recent years, there has been a growing interest in the study of polymorphic variants in infertile patients because their incidence, compared to the fertile population, is increased. However, most research has focused on the male patient study. Several studies have reported information about clinical outcomes, but the influence they may have on IVF laboratory procedures and embryo development has rarely been studied up to the blastocyst stage. In addition, it is very rare to find publications that show the study of polymorphisms according to their type or combination. Study design, size, duration Retrospective evaluation of a cohort of women who underwent autologous IVF cycles and karyotyping. The sample included 424 IVF cycles performed between July 2017-December 2021: control group (CG) with normal karyotype (211) and study group (SG) with polymorphisms (213). We studied the correlation between karyotype polymorphisms and laboratory outcomes in terms of: Number of Oocytes Retrieved, Fresh Oocyte Maturity (MII), Oocyte Survival after Thawing (TS), Fertilization (FZ), Oocyte Degeneration (OD) and Non-viable embryo rates. Participants/materials, setting, methods Analysis of the women karyotype, prior to the IVF cycle, was performed using the guidelines of the International System for Human Cytogenetic Nomenclature (ISCN). Differences between the different study groups (presence or absence of different chromosomal polymorphisms) were assessed with the appropriate statistical test according to the normality or non-normality of the variable distribution. Statistical analysis was performed using R statistical software (v.4.2.0) and SPSS (v.23.0, Chicago, IL, USA). Main results and the role of chance Average female age was 37.72 ± 3.98 (CG) and 36.73 ± 3.59 (SG). Average number of mature oocytes (MII) was: 6.45 ± 4.96(CG) and 7.59 ± 5.10 (SG). Statistically significant differences were found regarding the number of oocytes retrieved between the CG (8.14 ± 5.90) and the SG (9.53 ± 6.63) (p = 0.036), increasing when the ps+ variant was present (9.75 ± 7.21) (p = 0.045). However, no statistically significant differences were found between the presence of polymorphism (SG) and the CG in terms of: number of MII: 79.85% vs. 80.48% (p = 0.447), FZ: 73.76% vs. 70.49% (p = 0.352) and OD: 8.76% vs. 8.36% (p = 0.563) rates. In addition, the TS rate was statistically significant when there was the ps+ variant (82.95%) (p = 0.010) and/or combinations of more than one polymorphic variant (87.80%) (p = 0.044), compared to the CG (93.51%). Finally, according to embryo quality there was an increase in the non-viable embryos rate, on day 5 and/or day 6 of development, between the CG (34.17%) and the SG (43.02%) (p < 0.001), increasing when the ps+ variable was present (45.57%) (p < 0.001) and/or combinations of more than one polymorphic variant (p = 0.045). The results were corrected for confounding variables such as maternal age, oocyte origin and male factor variables, including polymorphic variants in the male karyotype. Limitations, reasons for caution Other variables that have not been analyzed may influence the outcomes. Larger prospective studies including homogeneous cohorts are needed in order to corroborate our initial results. Wider implications of the findings The polymorphic variants in the female karyotype, especially the “ps+” variant and the combination of multiple variants, could influence certain parameters in the laboratory. Therefore, it is important to request a karyotype to all patients before starting IVF treatment. Trial registration number NOT APPLICABLE

Human induced pluripotent stem cells derived from a patient with a mutation of SERPINC1 c.236G>A (p.R79H)

Mutation of SERPINC1 is related to the incidence of Inherited antithrombin (AT) deficiency. In this study, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a patient with a mutation of SERPINC1 c.236G>A (p.R79H). The generated iPSCs express pluripotent cell markers with no mycoplasma contamination. Besides, it has a normal female karyotype and could differentiate into all three germ layers in vitro.

Combination chromosome abnormaliries in girl with malformations of the large intestine

The purpose of the clinical case was to describe combination chromosome abnormaliries in girl with malformations of the large intestine.Girl A., 1, 9 year old was born prematurely. From birth, multiple stigmas of dysembriogenesis: poor weight gain, absence of an independent stool, marked delayed physical and psychomotor development attracted attention. During doppler echocardiography, a left-sided right- formed heart (chest), an open arterial duct, hemodynamically insignificant, with a diameter of about 1 mm is determined. In the second year of life, cholelithiasis was diagnosed (a single gallbladder concretion of 1.5 mm), erosive- hemorrhagic gastritis, subatrophic duodenoejunitis, an anomaly of the development of the large intestine (dolichosigma, dolichocolon) with hypomotor-type kolodiskinesia. During the examination, multiple stigmas of dysembriogenesis (oblique occiput, ocular hypotelorism, large, protruding auricles, strabismus, umbilical hernia), marked muscular hypotension, marked delayed physical and psychomotor development attract attention. Physical development: body length 70 cm, body weight 6650 g, teeth 8. SDS height –4.5, BMI 13.57 kg/m2, SDS –6.12. A molecular cytogenetic study revealed a normal female karyotype in proband’s mother, an abnormal karyotype 46, XX, der (21) t(4;21)(q31; q22) pat in proband’s mother, and a normal male karyotype with a balanced translocation 46, XX, t(4:21) in the patient’s father(q31: q22). The child has a chromosomal anomaly: partial trisomy of the q-arm of chromosome 4, as a result of translocation between chromosomes 4 and 21 of paternal inherited. Thus, the patient has an unbalanced karyotype, which causes a clinical features characterized by the marked delay in psychomotor and physical development, multiple stigmas of dysembriogenesis and malformations of the large intestine.