XY Mosaic Karyotype Research Articles

Complete or partial loss of the Y chromosome in an unselected cohort of 865 non-vasectomized, azoospermic men

BackgroundStructural abnormalities as well as minor variations of the Y chromosome may cause disorders of sex differentiation or, more frequently, azoospermia. This study aimed to determine the prevalence of loss of Y chromosome material within the spectrum ranging from small microdeletions in the azoospermia factor region (AZF) to complete loss of the Y chromosome in azoospermic men.ResultsEleven of 865 azoospermic men (1.3%) collected from 1997 to 2022 were found to have a karyotype including a 45,X cell line. Two had a pure 45,X karyotype and nine had a 45,X/46,XY mosaic karyotype. The AZF region, or part of it, was deleted in eight of the nine men with a structural abnormal Y-chromosome. Seven men had a karyotype with a structural abnormal Y chromosome in a non-mosaic form. In addition, Y chromosome microdeletions were found in 34 men with a structural normal Y chromosome. No congenital malformations were detected by echocardiography and ultrasonography of the kidneys of the 11 men with a 45,X mosaic or non-mosaic cell line.ConclusionsIn men with azoospermia, Y chromosome loss ranging from small microdeletions to complete loss of the Y chromosome was found in 6.1% (53/865). Partial AZFb microdeletions may give a milder testicular phenotype compared to complete AZFb microdeletions.

Do all women with turner syndrome with 45, X/46, XY mosaic karyotype need early gonadectomy?: Experience from an adult tertiary care centre

Do all women with turner syndrome with 45, X/46, XY mosaic karyotype need early gonadectomy?: Experience from an adult tertiary care centre

Complete Androgen Insensitivity Syndrome: A Rare Case with 47, XXY/46, XY Mosaic Karyotype and Literature Review

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disease caused by the absence or defects of androgen receptor (AR). Due to the insensitivity to androgen, clinically, patients often manifest as sexual development disorder.

CYTOGENETIC ANALYSIS OF PATIENTS WITH AMBIGUOUS GENITALIA

Objective: To determine the magnitude and classification of cases of ambiguous genitalia presenting to our setup.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Aug 2018 to Feb 2019.
 Methodology: All the patients with ambiguous genitalia referred for cytogenetic analysis, were included in the study. The patients were subjected to a detailed history and physical examination. The record of radiological investigations was were obtained. Cytogenetic analysis was performed using the conventional G-banding technique. Hormonal testing included 17- hydroxyprogesterone (17-OHP) levels was also performed.
 Results: Fifty-one cases of ambiguous genitalia were studied. The median age was 15 months. Thirty-three patients (64.7%) had a 46XY karyotype, 17 (33.3%) had a 46XX karyotype while 1 (1.9%) had 45X/46, XY mosaic karyotype. Thirty patients (58.8%) were products of consanguineous marriage. Congenital adrenal hyperplasia was diagnosed in 12 cases (70.5%) of 46 XX karyotype and in 3 cases (9%) of 46XY karyotype.
 Conclusion: Ambiguous genitalia, currently categorized as disorders of sex development, are not uncommon in our populartion. Increased awareness and early diagnosis are crucial to prevent life threatening complications of congenital adrenal hyperplasia, to determine sex of rearing, and to counsel the parents or patients.

Generation of an induced pluripotent stem cell line from an adult male with 45,X/46,XY mosaicism

Turner syndrome (TS) with 45,X/46,XY mosaic karyotype is a rare sex chromosome disorder with an occurrence of 0.15‰ at birth. We report the generation of an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a Chinese adult male with 45,X/46,XY mosaicism. The iPSC line retains the original 45,X/46,XY mosaic karyotype, expresses pluripotency markers and undergoes trilineage differentiation. Therefore, it offers an unprecedented cellular model to investigate the profound symptoms like infertility of TS in the male, and serve as a useful tool to develop therapies for the disease.

The Turner syndrome life course project: Karyotype‐phenotype analyses across the lifespan

Turner syndrome (TS) is associated with a variety of morbidities affecting nearly every body system, some of which increase in prevalence in adult life. The severity of clinical features in TS is roughly in parallel with the magnitude of the deficit of X-chromosome material. The aim of this study was to extend the established karyotype-phenotype relationships using data from a large adult cohort. Karyotypes were available in 656 women with TS. 611 of whom could be classified into five major groups within the cohort: 45,X; 45,X mosaicism (45,X/46,XX); isochromosome X (isochromosome Xq); mosaicism 45,X/46,XY and ringX. Continuous variables such as blood pressure and biochemical markers from clinic data were binarised allocating those in the upper quartile to represent at-risk individuals. With the exception of bone mineral density T-score for which the lower quartile was allocated as at risk. For comorbidities, initiation of formal treatment was recorded. 45,X/46,XX had considerably lower frequency of comorbidities compared to 45,X. The isochromosome group experienced similar outcomes to 45,X. Novel associations were found between the XY mosaic karyotype group and a decreased prevalence of thyroid disease and severe hearing loss. A previously unreported increased incidence of metabolic syndrome was noted within the ring chromosome subgroup. Karyotype may play an important factor against stratifying risk of comorbidity in TS and should be taken into consideration when managing adults with TS. Further investigations of the isochromosome (Xq) and ring groups are necessary to further clarify their associations with comorbidities.

Meiotic behaviour and sperm aneuploidy in an infertile man with a mosaic 45,X/46,XY karyotype

The meiotic behaviour of the germ cells in 45,X/46,XY men has not been extensively studied. This study investigated the meiotic events and sperm aneuploidy in an azoospermic man with a 45,X/46,XY (50/50) mosaic karyotype to better understand the fate of the 45,X cells and the production of chromosomally abnormal spermatozoa. Combining immunofluorescence techniques and fluorescence in-situ hybridization, meiotic recombination, synapsis, meiotic sex chromosome inactivation (MSCI) and configuration were analysed, as well as sperm aneuploidy in the patient and 10 normal, fertile men. Despite the 50:50 somatic mosaicism in the patient, 25% of pachytene cells analysed were 45,X. Furthermore, 63% of pachytene cells were 46,XY with paired sex chromosomes, and 12% were 46,XY with unpaired sex chromosomes, which displayed abnormal MCSI patterns. Although the patient's testicular spermatozoa showed increased aneuploidy, the majority were of normal constitution. The X:Y sperm ratio was significantly increased compared with the controls (P < 0.001), which may indicate that some 45,X cells gave rise to X-bearing spermatozoa. The findings provide insight into the fate of 45,X/46,XY cells in meiosis, supporting the hypothesis that stringent checkpoints ensure the favourable production of spermatozoa with normal chromosomal constitution despite an individual's abnormal karyotype.

Clinical features and Y chromosomal abnormalities in patients with karyotype chimerism of 45, XO/46, XY

Objective To increase the knowledge of clinical features and Y chromosomal abnormalities in patients with mosaic karyotype 45,XO/46,XY.Methods The clinical features,peripheral lymphocyte karyotype,sex hormones,treatment,and follow-up information were retrospectively reviewed.Results (1) 7 patients with 45,XO/46,XY were included.Their social gender was 3 male and 4 female,and the age by diagnosis was (14 ± 3) years (range 11-20 years).(2) Patients presented with short stature (n =7) and other specific somatic signs similar to Turner's syndrome.(3) The external genitalia varied from complete male to complete female manifestations.There were normal penis (n =1),hypospadia (n =2),enlarged clitoris and combined opening with ureter and vagina (n =1),and wholesome vagina opening (n =3).By physical examination and ultrasound,testes were detected in 3 patients,1 patient had testes and ovary-like gonad,and 1 had ovary-like gonad,and no gonads were detected in 2 patients.(4) Among 7 patients,4 had obviously abnormal Y chromosome.1 patient had micro-deletion on Y chromosome by Multiplex Ligation Dependent Probe Amplification (MLPA).(5) 4 patients had therapy with (rhGH).Gonads were removed from P4,showing ovary-like tissue.3 patients received sex hormone replacement.Conclusion Patients with 45,XO/46,XY mosaic karyotype manifest short stature and other clinical features of Turner's syndrome.The presence of testis may result in different extent of virilization.The mosaic karyotype and failure of spermatogenesis may be caused by abnormal Y chromosome.Treatment includes rhGH therapy,removal of dysgenic gonads and hormonal replacement. Key words: 45, XO/46, XY ; Turner's syndrome ; Karyotype ; Y chromosome

A Case of Ambiguous External Genitalia in a Thoroughbred Male Horse with the 63,XO/64,XY Mosaic Karyotype

A Thoroughbred colt with ambiguous external genitalia was presented for clinical and histological examinations. The colt had a short penis that faced backward between his hind limbs. The measurements of luteinizing hormone, follicle stimulating hormone, testosterone and ir-inhibin showed a tendency to increase gradually from April. Both the sex-determining region of the Y chromosome and amelogenin gene fragments were detected by the PCR method. A cytogenetic analysis revealed the 63,XO/64,XY mosaic karyotype (ratio 83:17). In autopsy, immature symmetrical subcutaneous testes were found in the inguinal regions. The testes and other accessory sex organs were histologically normal. These results add to our knowledge of chromosomal abnormality and information concerning disorders of sex development in the horse.

Assisted Reproductive Treatment Applications in Men With Normal Phenotype But 45,X/46,Xy Mosaic Karyotype: Clinical and Genetic Perspectives

The 45,X/46,XY mosaic karyotype is expressed by a spectrum of genital phenotypes, ranging from normal males through to ambiguous genitalia and to normal females. We present three cases of men with azoospermia or severe oligozoospermia, and a 45,X/46,XY mosaic karyotype and two with a Y-chromosome microdeletion. Phenotypically, they appeared as normal males, with normal penis, scrotum and secondary sex characteristics. Testicular sperm extraction and aspiration were applied to patients, and couples were prepared for assisted reproductive therapy. All men with azoospermia or severe oligozoospermia were evaluated for karyotype and Y-chromosome microdeletion even if they had normal phenotypes. Possibilities for finding sperm and the biologic paternity in subjects with 45,X/46,XY karyotype should be considered. Furthermore, the increased risk for testicular neoplasia with mosaic karyotypes should be taken into consideration.

Synchronous Bilateral Breast Carcinoma in a 50-Year-Old Man with 45,X/46,XY Mosaic Karyotype: Report of a Case

We report a case of synchronous bilateral breast cancer in a patient with ambiguous external genitalia attributed to a 45,X/46,XY mosaicism. To our knowledge, this represents the first such case ever to be reported. Mammography, ultrasonography, computed tomography, and magnetic resonance imaging all showed bilateral suspicious breast masses with microcalcifications. There were no radiological findings of muscle invasion or axillary lymphadenopathy. The patient was successfully treated by bilateral radical modified mastectomy followed by external irradiation and adjuvant endocrine therapy. Histological examination revealed a bilateral ductal carcinoma in situ, with a cribriform and papillary pattern and microfoci of infiltrating ductal carcinoma. The hormonal profile revealed high levels of follicle-stimulating hormone and luteinizing hormone, and low levels of testosterone. Testicular sonography revealed small hypoechoic testicles with bilateral microlithiasis. This case shows that 45,X/46,XY men may have an increased risk of breast cancer and must be followed up carefully.

Three New Novel Point Mutations Localized within and Downstream ofHigh-Mobility Group-boxRegion inSRYGene in Three Indian Females with Turner Syndrome

Point mutations and deletions in the SRY gene result in XY sex reversal in pure gonadal dysgenesis. To date, a majority of these affect the high-mobility group (HMG) domain of SRY, which plays a key role in its DNA binding activity. We carried out molecular genetics studies in three Turner syndrome patients all presenting with 45,X/46,XY mosaic karyotype. Case 1 demonstrated an insertion of T (thymine) within helix I of HMG box leading to frame shift mutation (N82X). In case 2, insertion of A (adenine) downstream of HMG box resulted in a nonsense frame shift mutation (L159fsX167). These mutations resulted in truncated and altered proteins. In case 3, G>C missense mutation is found at codon 74 within helix I of HMG box (Q74H). No other mutations were found in the SRY gene of these patients. An allele-specific oligonucleotide study further confirmed that these variants are not common polymorphisms. To our knowledge, this is the first time these mutations are described at these codons resulting in mutated SRY proteins. Lack of a second sex chromosome in a majority of cells [mosaic karyotype and mutation(s) in the SRY gene] in these patients may have triggered the short stature.

Seminoma and a gonadoblastoma in an infant with mixed gonadal dysgenesis

The genital examination of a newborn with ambiguous genitaliarevealedanenlargedphallicstructure,asingleanterior perineal opening, and fused labioscrotal folds with no palpable gonads (Fig 1). No Turner syndrome stigmata were present. The testosterone level was 29 ng/dL (normal range for female newborns, 20-64 ng/dL; males, 75-400 ng/dL), and a mullerian inhibitory substance was undetectable. Chromosome analysis revealed a 45,X/46,XY mosaic karyotype. A normal uterus and kidneys were identified by ultrasonogram, and a urogenital sinus was present on cystourethrogram. The family selected a female gender for the baby. At9monthsofage,theinfanthadbilateralgonadectomy and feminizing genital surgery. Intraoperative findings confirmed a low confluence urogenital sinus with a well-formed vagina. A streak gonad with a normal fallopian tube and hemiuterus were present on the right. The left gonad was torsed and free-floating in the abdomen without identifiable ductal structures. Pathologic examination of the right gonad showed a testis-streak with seminiferous tubules containing placental alkaline phosphatase-positive (PLAP) cells, consistent with intratubular germ cell neoplasia, and peripheral streak gonadal tissue with multifocal areas of gonadoblastoma (Fig 2, B). The left gonad consisted of an encapsulated 2.0 3 1.8 3 0.6 cm soft tissue mass with diffuse coagulative necrosis and dystrophic calcifications consistent with torsion. Sheets of monomorphic large round cells surrounded by fibrous septae (Fig 2, A) were identified, consistent with a seminoma. A computed tomography scan of the abdomen, pelvis, and chest showed no evidence of metastasis. Beta-human chorionic gonadatropin and a-fetoprotein levels were normal. We describe a unique case of bilateral gonadal tumors occurring in an infant with mixed gonadal dysgenesis (MGD). MGD is an intersex disorder characterized by asymmetric dysgenetic gonads, ambiguous genitalia, persistent mullerian structures, and a Y cell line. Patients with MGD are at high risk of developing gonadal tumors, the majority being identified in the second and third decade of life. The most common tumor is a gonadoblastoma, a benign lesion composed of dysplastic germ and sex cord cells. However, the germ cell element can give rise to malignant germinomas such as seminomas, as in our case. 1,2 Prophylactic gonadectomy is indicated, but there are no clear recommendations as to when this should occur. The young age of this child emphasizes the importance of very early gonadectomy in patients with MGD that are to be raised in the female gender, and careful monitoring of male infants after early orchiopexy.

Ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions in a 17-year-old man

Objective: To describe clinical and laboratory features of a patient with 45,X/46,XY mosaic karyotype and Y chromosome microdeletions and to discuss the diagnostic problems in his management. Design: Case report. Setting: University department. Patient(s): A 17-year-old man with ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions. Intervention(s): Testicular ultrasonography, karyotype, open testicular biopsy, polymerase chain reaction (PCR) screening for cystic fibrosis, PCR screening for Y chromosome microdeletions in peripheral blood and testicular tissue, and reverse transcriptase PCR in testicular tissue for Y chromosome microdeletions. Main Outcome Measure(s): Avoidance of dissemination of testicular cancer. Result(s): The patient was referred for bilateral orchiectomy. Conclusion(s): 45,X/46,XY mosaic karyotype is associated with a broad spectrum of phenotypes that includes female with Turner syndrome, male with mixed gonadal dysgenesis, male pseudohermaphroditism, and apparently normal male. Microdeletions of the long arm of the Y chromosome may be associated with Y chromosomal instability, leading to formation of 45,X cell lines. 45,X/46,XY males carry an increased risk for gonadal tumors and must be followed closely.