Medical Genetics Center Research Articles

Evaluation of Cardiomyopathy-Related Target Genes by Next-Generation Sequencing Method and Investigation of the Phenotype-Genotype Relationship

Background: Primary heart muscle diseases called cardiomyopathy (CMP) constitute an important group of subsequent heart disorders. CMPs are basically divided into four subgroups associated with the heart muscle but clinically distinguishable: hypertrophic CMP (HCM), dilated CMP (DCM), restrictive CMP (RCM), and left ventricular non-compaction CMP. Material and Methods: The results of the patients who applied to the Genetic Diseases Evaluation Center with the preliminary diagnosis of clinical CMP were evaluated retrospectively in the current study. In the current study, 103 cases were included and evaluated for phenotype-genotype association with the CMP next-generation sequencing (NGS) panel. Results: Fifty-eight different variants were identified in 45 patients. Sixteen out of those 58 variants were novel. Of these variants, 19 (32.75%) were likely pathogenic (LP)/pathogenic (P), and 35 (60.34%) were variants of uncertain significance. Conclusion: The prevalence of pathogenic variants in target genes associated with CMP is important for our current country's population, and multiple gene groups associated with CMP can be screened through NGS. The contribution rate to the clinical diagnosis was 18.44% in terms of the individual population who applied to our medical genetics center and were compatible with the CMP indication.

Tribal Founder EMC1 Variant in 5 Kuwaiti Families Expands Phenotypic Spectrum of EMC1-Related Disorder.

The endoplasmic reticulum (ER) membrane protein complex is a conserved multisubunit transmembrane complex that enables energy-independent insertion of newly synthesized membrane proteins into ER membranes, mediating protein folding, phospholipid transfer from ER to mitochondria, and elimination of misfolded proteins. The first subunit of EMC (EMC1) is encoded by EMC1. Both monoallelic de novo and biallelic EMC1 variants have been identified to cause cerebellar atrophy, visual impairment, and psychomotor retardation (CAVIPMR) [OMIM #616875]. Eight families with biallelic EMC1 variants and CAVIPMR have been reported. Here, we describe 8 individuals from 5 Kuwaiti families from the same tribe, with the previously reported homozygous pathogenic missense EMC1 variant [c.245C>T:p.(Thr82Met)] and CAVIPMR. Proband exome sequencing was performed in 3 families, while targeted molecular testing for EMC1 [c.245C>T:p.(Thr82Met)] variant was performed in the other 2 families based on strong clinical suspicion and tribal origin. Sanger sequencing confirmed variant segregation with disease in all families. We identified 8 individuals from 5 Kuwaiti families with the homozygous pathogenic EMC1 variant [c.245C>T:p.(Thr82Met)] previously reported in a Turkish family with CAVIPMR. The variant was absent from Kuwait Medical Genetic Center database, thus unlikely to represent a population founder allelic variant. The average age at symptom onset was 11 weeks, with all families reporting either visual abnormalities, hypotonia, and/or global developmental delay (GDD) as the presenting features. Shared clinical features included GDD (8/8), microcephaly (8/8), truncal hypotonia (8/8), visual impairment (7/7), and failure to thrive (7/7). Other common features included hyperreflexia (5/6; 83%), peripheral hypertonia (3/5; 60%), dysmorphism (3/6; 50%), epilepsy (4/8; 50%), and chorea (3/8; 36%). Brain imaging showed cerebellar atrophy in 4/7 (57%) and cerebral atrophy in 3/6 (50%) individuals. The presence of exact biallelic homozygous EMC1 variant in 5 Kuwaiti families from the same tribe suggests a tribal founder allelic variant. The clinical features in this study are consistent with the phenotypic spectrum of EMC1-associated CAVIPMR in previous reports. The presence of chorea, first noted in this study, further expands the phenotypic spectrum. Our findings emphasize the importance of targeted EMC1 variant [c.245C>T:p.(Thr82Met)] testing for infants from affected tribe who present with visual impairment, GDD, and hypotonia.

Survey of patient satisfaction with genetic counseling services in Korea.

Since the 1990s, genetic clinics have been established in South Korea, enabling the provision of clinical genetics services. However, genetic counseling services are not widely used in the medical system. In contrast, recently, the demand for genetic counseling has increased due to the rapid development of genomic medicine. Therefore, it is important for medical geneticists and genetic counselors to collaboratively provide genetic counseling services. This study aimed to evaluate the perception and satisfaction of patients with rare genetic diseases and their families regarding genetic counseling services provided by a genetics team at the medical genetics center of a tertiary general hospital for rare genetic diseases. From April to November 2021, a survey was conducted with 203 individuals, including 111 and 92 individuals in the patient and family groups, respectively. Overall, 164 individuals (80.8%) responded that they were aware of genetic counseling services, and 135 individuals (66.5%) responded that they were aware of the role of genetic counselors. Patients and their families wanted to receive information about the following from genetic counseling: clinical manifestation and prognosis of the diagnosed disease (78.8%), treatment and management of the disease (60.6%), risk of recurrence within the family (55.7%), treatment options and alternatives for family and prenatal testing, and various support services. The score of satisfaction with genetic counseling services provided by the genetics team was 8.19 ± 1.68 out of 10. Patients with rare genetic diseases and their families were satisfied with genetic counseling services regarding their diseases, test results, and treatment options. Moreover, the patients could receive psychosocial support and referrals to other medical service providers and support services. As a genetic team approach, collaboration between medical geneticists and certified genetic counselors would be useful in providing information and in diagnosing, treating, and managing patients.

Lysosomal storage diseases. Sphingolipidoses – leukodystrophy

Lysosomal storage diseases. Sphingolipidoses – leukodystrophy

Exome Sequencing for the Diagnostics of Osteogenesis Imperfecta in Six Russian Patients.

Osteogenesis imperfecta (OI) is a group of inherited disorders of connective tissue that cause significant deformities and fragility in bones. Most cases of OI are associated with pathogenic variants in collagen type I genes and are characterized by pronounced polymorphisms in clinical manifestations and the absence of clear phenotype-genotype correlation. The objective of this study was to conduct a comprehensive molecular-genetic and clinical analysis to verify the diagnosis of OI in six Russian patients with genetic variants in the COL1A1 and COL1A2 genes. Clinical and laboratory data were obtained from six OI patients who were observed at the Medical Genetics Center in Saint Petersburg from 2016 to 2023. Next-generation sequencing on MGISEQ G400 (MGI, China) was used for DNA analysis. The GATK bioinformatic software (version 4.5.0.0) was used for variant calling and hard filtering. Genetic variants were verified by the direct automatic sequencing of PCR products using the ABI 3500X sequencer. We identified six genetic variants, as follows pathogenic c.3505G>A (p. Gly1169Ser), c.769G>A (p.Gly257Arg), VUS c.4123G>A (p.Ala1375Thr), and c.4114A>T (p.Asn1372Tyr) in COL1A1; and likely pathogenic c.2035G>A (p.Gly679Ser) and c.739-2A>T in COL1A2. In addition, clinical cases are presented due to the presence of the c.4114A>T variant in the COL1A2 gene. Molecular genetics is essential for determining different OI types due to the high similarity across various types of the disease and the failure of unambiguous diagnosis based on clinical manifestations alone. Considering the variable approaches to OI classification, an integrated strategy is required for optimal patient management.

Relationship of thymic area with clinical-epidemiological variables and values of T-lymphocyte subpopulations in peripheral blood of children with recurrent infections

BackgroundRecurrent infections in childhood are the main cause of remission to the immunology service. T lymphocytes generated in the thymus are essential for fighting infection, making the thymus area an important predictor of the immune system’s competence. This study aimed to identify the possible relationship of the thymic area with clinical-epidemiological variables and values of subpopulations of T lymphocytes in the peripheral blood of children with recurrent infections.MethodsWe conducted applied research using a transversal analytical design at the National Medical Genetics Center (Havana, Cuba), from January to August 2022. The study covered 73 children of which we analyzed clinical-epidemiological variables and the size of the thymus through ultrasound. Furthermore, we determined the relative and absolute values of the subpopulations of T cells using flow cytometry.ResultsOf the children studied, 65.8% had thymic hypoplasia. The children who breastfed for less than 6 months showed four times the risk of developing moderate-severe thymus hypoplasia (OR = 3.90, 95% CI: 1.21–12.61). A direct relationship was found between the area of the thymus and the child’s size (r = 0.238, p = 0.043) and weight (r = 0.233, p = 0.047). The relative values of CD3+ T lymphocytes decreased in the cases of mild hypoplasia (p = 0.018) and moderate-severe hypoplasia (p = 0.049). The thymus area was associated with the absolute cell count of CD8+ effector memory T cells (rs = −0.263, p = 0.024) and of the central memory T cells (r = −0.283, p = 0.015).ConclusionsBreastfeeding for less than 6 months, as well as the weight and size of the child, are related to their thymus area. The subpopulation values of T lymphocytes detected suggest that patients with thymic hypoplasia develop a contraction of CD3+ T cells, which can make them more vulnerable to infectious processes. This finding was combined with an expansion of the memory compartments of the subpopulations of CD8+ T cells, suggesting a greater susceptibility to intracellular viral and bacterial infections in these cases.

5 P consortium “Children’s Medicine”

Medical consortia help solve current healthcare problems. Four scientific medical institutions (GBUZ of the Moscow region “Research Institute of Childhood of the Ministry of Health of the Moscow Region”, Scientific Research Clinical Institute of Pediatrics and Pediatric Surgery named after Academician Yu. E. Veltishchev Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N. I. Pirogov” of the Ministry of Health Russia, the Federal State Budgetary Institution “Medical Genetic Research Center named after Academician N. P. Bochkov”, the Federal Budgetary Institution “Moscow Research Institute of Epidemiology and Microbiology named after G. N. Gabrichevsky” of Rospotrebnadzor) and one higher educational institution (the Federal State Budgetary Educational Institution of Higher Education “Ural State Medical University” of the Ministry of Health of the Russian Federation) united into the 5P “Children’s Medicine” consortium to solve pressing problems of children’s healthcare in accordance with the basic principles of personalized medicine. Organizing large congresses with international participation dedicated to the problems of children’s healthcare is an opportunity for doctors in the Russian Federation and other countries to share knowledge and best practices on saving a child’s life and treating diseases from an early age of the patient through direct communication. A systematic approach can be considered the most effective for solving problems in all areas, including children’s healthcare, and the 5 P “Children’s Medicine” congress helps doctors go beyond the boundaries of the familiar and familiar, learn new things, and get ideas for further professional growth.

Novel ERLIN2 variant expands the phenotype of Spastic Paraplegia 18.

The Brazilian Northeast region is notable for its high prevalence of consanguineous marriages and isolated populations, which has led to a significant prevalence of rare genetic disorders. This study describes the clinical presentation of four affected individuals from the same family, comprising two siblings and their cousins, with ages ranging from 11 to 20years. In a small and isolated community in Northeastern Brazil, affected individuals initially underwent a clinical assessment. Subsequently, written consent was obtained from their legal guardians, and an extensive clinical evaluation was conducted at a medical genetics center. Family data provided the basis for constructing the pedigree, and biological samples (blood or oral swabs) were collected from both affected and unaffected family members. Following informed consent from one patient, Whole Exome Sequencing (WES) was carried out, encompassing exome sequencing, assembly, genotyping, and annotation. A potentially deleterious variant was then singled out for further segregation analysis through Sanger Sequencing, involving both the proband and select family members. These individuals exhibit severe neurodevelopmental delays, encompassing symptoms such as spastic paraplegia, neuropathy, intellectual impairments, and language challenges. Through next-generation sequencing (NGS) techniques, a previously unreported homozygous variant within the ERLIN2 gene linked to spastic paraplegia 18 (SPG18) was identified across all four patients. Also, all patients displayed childhood cataract, expanding the known clinical spectrum of SPG18.

Biotin-thiamine responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of cases in Kuwait with novel variants

BackgroundBiotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive neurometabolic disorder that is caused by biallelic pathogenic SLC19A3 variants and is characterized by subacute encephalopathy associated with confusion, convulsions, dysphagia, dysarthria, or other neurological manifestations.MethodsA retrospective review of the data registry in Kuwait Medical Genetics Center for all cases diagnosed clinically and radiographically and confirmed genetically with BTBGD.ResultsTwenty one cases from 13 different families were diagnosed with BTBGD in Kuwait. Most cases (86%) presented with confusion, dystonia, convulsions, or dysarthria, while three individuals were diagnosed pre-symptomatically during familial targeted genetic screening. Symptoms resolved completely within 2-week of treatment in two-thirds of the symptomatic cases but progressed in six of them to a variety of severe symptoms including severe cogwheel rigidity, dystonia and quadriparesis due to delayed presentation and management. Neuroradiological findings of the symptomatic cases revealed bilateral central changes in the basal ganglia. Two novel homozygous missense SLC19A3 variants were detected in a Kuwaiti and a Jordanian individuals, in addition to the previously reported Saudi founder homozygous variant, c.1264A > G; p.(Thr422Ala) in the remaining cases. Age of diagnosis ranged from newborn to 32 years, with a median age of 2–3 years. All cases are still alive receiving high doses of biotin and thiamine.ConclusionThis is the first study reporting the phenotypic and genotypic spectrum of 21 individuals with BTBGD in Kuwait and describing two novel SLC19A3 variants. BTBGD is a treatable neurometabolic disease that requires early recognition and treatment initiation. This study highlights the importance of performing targeted molecular testing of the founder variant in patients presenting with acute encephalopathy in the region.

Genetic analysis of a child with Pitt-Hopkins syndrome due to a novel variant of TCF4 gene derived from low percentage maternal mosaicism

To explore the genetic etiology of a child with Pitt-Hopkins syndrome. A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Karyotype analysis was also carried out for the child, and her mother was subjected to ultra-deep sequencing and prenatal diagnosis upon her subsequent pregnancy. The clinical manifestations of the proband included facial dysmorphism, Simian crease, and mental retardation. Genetic testing revealed that he has carried a heterozygous c.1762C>T (p.Arg588Cys) variant of the TCF4 gene, for which both parents had a wild-type. The variant was unreported previously and was rated as likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Ultra-deep sequencing indicated that the variant has a proportion of 2.63% in the mother, suggesting the presence of low percentage mosaicism. Prenatal diagnosis of amniotic fluid sample suggested that the fetus did not carry the same variant. The heterozygous c.1762C>T variant of the TCF4 gene probably underlay the disease in this child and has derived from the low percentage mosaicism in his mother.

Whole exome sequencing analysis and prenatal diagnosis in children with neurodevelopmental disorders

To explore the application value of whole exome sequencing (WES) in the diagnosis of prenatal and postnatal neurodevelopmental disorders (NDDs). A total of 70 patients diagnosed with NDDs who underwent WES at the Medical Genetics Center of the Maternal and Child Health Hospital of Hubei Province between June 2020 and July 2021 were retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples and amniotic fluid. WES-based copy number variant (CNV) analysis was integrated into the routine WES data analysis pipeline. The results showed that a molecular diagnosis rate could be made in 21/70 (30%) cases. Of 21 positive cases, 14 (23%) cases were detected by single-nucleotide variant/small insertion/deletion (SNV/Indel) analysis, of which 12 variants were novel, 6 (9.8%) cases were detected by WES-based CNV analysis, and 1 (1.6%) case was detected by a combination of both. The diagnostic yield of WES combined with CNV analysis was higher than that of SNV/Indel analysis alone (30%, 21/70 vs. 20%, 14/70). Of the 28 prenatally diagnosed cases, 6 cases were found to have inherited parental variation for NDDs, 10 cases were found not to have the same pathogenic variation as the proband, and the remaining 12 cases were found to have no pathogenic or likely pathogenic variation that could explain the NDDs phenotype. Clinical follow-up showed that 5 families opted for abortion and the remaining had no current abnormalities. In conclusion, WES may be an effective method to clarify the genetic etiology and prenatal diagnosis of NDDs, which is helpful in assessing the prognosis to aid clinical management and reproductive guidance.

Retrospektyvnyi analiz spektra pryrodzhenykh vad rozvytku, vyznachenykh antenatalno u Lvivskomu medyko-henetychnomu tsentri (2018–2020)

Introduction. According to the WHO, about 3 % of infants worldwide are born with a congenital malformation (CM). The aim of the study. To conduct a retrospective analysis of the spectrum of congenital malformations diagnosed during pregnancy based on the Lviv Medical Genetics Center during 2018-2020 yy. Materials and methods. Clinical and epidemiological, as well as medical and statistical data on CM diagnosed prenatally between 2018-2020 were collected from primary source documents (Form No. 49) and then analyzed at the Lviv Medical Genetics Center ʺInstitute of Hereditary Pathology, National Academy of Medical Sciences of Ukraineʺ, Lviv. The Student’s t-test was used to determine the difference between the arithmetic means. The null hypotheses were tested using a t-test at the significance level of p-value less than 0.05. Results. A total of 11062 pregnant women were examined between 2018-2020: CM at different stages of pregnancy were diagnosed in 454 cases, which accounted for 4.1 % of cases and did not exceed the population value. There was a 2.3-fold reduction in the number of pregnant women presented to the Medical Genetics Center in 2020, probably due to the global coronavirus pandemic – from 5007 women in 2018 to 2212 females in 2020. However, the number of CM diagnosed prenatally in 2020 was not statistically significant (p-value more than 0.05) as compared to the average value for these years and 2018. In 2018, a total of 5007 pregnant women were examined at the Lviv Medical Genetics Center. In 136 (4.8 %) cases, fetal malformations were diagnosed before 22 weeks of gestation, while in 26 (1.2 %) cases, pregnancy was affected by congenital anomaly in its second half. In 2019, there were examined 3843 pregnant women. In169 (7.8 %) cases, CM were diagnosed before 22 weeks of gestation, that was statistically significant as compared to 2018 (p-value less than 0.05) and in 20 (1.2 %) cases, fetal anomalies were detected in the second half of pregnancy, that was not statistically significant as compared to the previous year (p-value more than 0.05). In 2020, we examined 2212 pregnant women. Reducing the number of visits to our medical center was probably due to the coronavirus pandemic. There were95 (5.0 %) cases of fetal malformations diagnosed before 22 weeks of gestation and 8 (2.5 %) cases of congenital anomalies detected in the second half of pregnancy. The number of CM diagnosed prenatally was the highest in 2019 – 4.9 %; however, there was no statistically significant difference (p-value more than 0.05) in the average values for these years – 4.1 % and 3.2 % in 2020 and 2018, respectively. In 2020, the incidence of congenital malformations diagnosed after 22 weeks of gestation was significantly higher (p-value less than 0.05) than in other years – 2.5 % and 1.2 %, respectively. Conclusions. Between 2018-2020, the incidence of congenital malformations diagnosed at different stages of pregnancy was 4.1 %. Congenital malformation s of the nervous system (Q00-Q07) were the most common anomalies diagnosed before 22 weeks of gestation, while after 22 weeks, the most common malformations were congenital malformations of the urinary system (Q60-Q64). Qualified timely diagnosis of correctable developmental deficiencies, as well as team efforts of obstetricians, neonatologists, pediatric neurologists, pediatricians, and other health care professionals to ensure normal childbirth and provide a baby with specialized care, followed by life-time rehabilitation are the main tasks of prenatal medicine.

Ovarian hyperstimulation syndrome in assisted reproductive technology programs in the ­Republic of Bashkortostan

Background. Ovarian hyperstimulation syndrome is a fatal complication of unknown etiology. In connection with the increase in the frequency of this complication, it is necessary to identify prognostically significant markers to discover the risk of its development.
 Aim. To analyze the frequency of ovarian hyperstimulation syndrome and search for the association of genes for differential growth factor 9, luteinizing hormone/horiogonadotropin receptor, and follicle-stimulating hormone receptor with different responses to ovulation stimulation.
 Material and methods. A retrospective single-center cohort study of the frequency and clinical parameters of early ovarian hyperstimulation syndrome was carried out in 147 patients, the average age was 36.5 [3338] years, who underwent an in vitro fertilization program in the period 20062021 in the Department of Assisted Reproductive Technologies of the Republican Medical Genetic Center in Ufa. The study of polymorphic loci of the genes for differential growth factor 9, luteinizing hormone/choriogonadotropin receptor, and follicle-stimulating hormone receptor was performed using TaqMan technology and real-time polymerase chain reaction. Deoxyribonucleic acid was isolated from peripheral blood samples. Statistical analysis was performed using the KruskalWallis criteria, median test, Pearson's 2 test, using the Statistica 12 software package.
 Results. 7577 procedures of assisted reproductive technologies were performed. 147 (2.3%) cases of ovarian hyperstimulation syndrome were registered, 53 (0.8%) cases of moderate and severe degree, 84 (1.3%) cases of mild degree. The *CT genotype of the rs254286 polymorphic locus of the differential growth factor 9 gene was associated with a poor ovarian response 15 (0.75); (2=4.00; p=0.02; odds ratio 3.4; 95% confidence interval 1.1310.27). The distribution of allele and genotype frequencies of the other studied genes did not differ statistically significantly in all the studied groups.
 Conclusion. The frequency of ovarian hyperstimulation syndrome in the Republic of Bashkortostan was 2.3%; the *CT genotype of the rs254286 polymorphic locus of the differential growth factor 9 gene, as well as the level of anti-Mllerian hormone, can serve as markers of a poor response and ovarian hyperstimulation to ovulation stimulation.

Analysis of the number of registered patients whis rare diseases in some regions of Ukraine

Rare (orphan) diseases (RD) are a global priority for health systems. In Europe, including Ukraine, the disease is considered rare with a prevalence of 1 patient per 2,000 population. To date, by the orphanet data, 6,172 unique rare diseases have been discovered. An important issue today is the understanding and analysis of data on the prevalence of RD in Ukraine, which will effectively plan the need for therapy and predict its cost.
 Aim of the investigation was to analyze the available data on the of the registered cases of orphan diseases among children and adults in all Ukraine’s regions and determining the share of each disease in the overall structure in terms of age group of patients.
 The object of the in vestigation are data of the Department of Statistics of the Ministry of Health on the cases of rare diseases, that were registered in Ukraine as of January 2020 and Medical Genetics Center’s data. The study was conducted using informative methods of analysis (collection and data processing), systematization and generalization, mathematical and statistical calculations.
 According to the Сenter’s of Medical Statistics of the Ministry of Health data the total number of registered patients was 10786 patients, of whom children accounted for 54%. Among given diseases the largest proportion of patients had been registered with a diagnosis of «juvenile rheumatoid arthritis» – 2,291 patients, most of whom, almost 80%, are children. Among 18 rare diseases, 11%, were registered only among pediatric patients: Pump's disease, Fabri's disease. It has been established that Kyiv, Poltava, Dnipro, Ivano-Frankivsk and Kharkiv regions had been characterized by the highest total number of orphan patients. Regions with the lowestregistered number of orphan patients – are Luhansk, Lviv, Kherson, Sumyand Volyn. There was no information on registered RDs in Chernivtsi, Odesa, Zakarpattia regions and Kyiv city from the Center for Medical Statistics of the Ministry of Health, but it was indicated the cases of four RDs in Odessa region and Kyiv city by newborn screening program in 2020, that has shown problems in the collection, centralization and coordination of the statistic information of RDs and needs to be resolved in the future at the state and regional levels.

Identification of FOXG1 mutations in infantile hypotonia and postnatal microcephaly.

FOXG1, located at chromosome 14q12, is critical for brain development, and patients with FOXG1 mutation exhibit developmental encephalopathy with high phenotypic variability, known as FOXG1 syndrome. Here, we report 3 cases of FOXG1 syndrome that presented with infantile hypotonia and microcephaly.A total of 145 children with developmental delay and/or hypotonia were evaluated by whole-exome sequencing (WES) in the pediatric neurology clinic and medical genetics center at Asan Medical Center Children's Hospital, from 2017 to 2019. Each FOXG1 mutation was confirmed by Sanger sequencing. The clinical findings of each patient with FOXG1 mutation were reviewed.WES identified de-novo, pathogenic, and heterozygous FOXG1 mutations in 3 of 145 patients in our patient cohort with developmental delay and/or hypotonia. The characteristics of brain magnetic resonance imaging (MRI) were reported as callosal anomaly, decrease in frontal volume, fornix thickening, and hypoplastic olfactory bulbs. A phenotype-genotype correlation was demonstrated as a patient with a novel missense mutation, c.761A > C (p.Tyr254Ser), in the forkhead domain had better outcome and milder brain abnormalities than the other 2 patients with truncating mutation in the Groucho binding domain site, c.958delC (p.Arg320Alafs), or N-terminal domain, c.506dup (p.Lys170GlnfsThe). Importantly, all 3 patients had hypoplastic olfactory bulbs on their brain MRI, which is a distinct and previously unrecognized feature of FOXG1 syndrome.This is the first report of FOXG1 syndrome in a Korean population; this condition accounts for 2% (3 of 145 patients) of our patient cohort with developmental delays and/or hypotonia. Our report contributes to understanding this extremely rare genetic condition in the clinical and genetic perspectives.

Molecular Cytogenetic Characterization of Synovial Sarcoma Cell Line SW982

Novel Approaches in Cancer Study Molecular Cytogenetic Characterization of Synovial Sarcoma Cell Line SW982 Na Du1,2, Wanguo Bao1, Kaiyu Zhang1, Xianglan Lu2, Guangming Liu2,3, Chuan Zhang2,4, Yunpeng Shi2,5, Ming Li2,6, Rebecca Crew2, Xianfu Wang2 and Feng Wang1* 1Department of Infectious Diseases, China 2Department of Pediatrics, USA 3Department of Gastroenterology, China 4Gansu Province Medical Genetics Center, China 5Department of Hepatobiliary and Pancreatic Surgery, China 6Department of Neurology, China *Corresponding author:Feng Wang, Department of Infectious Diseases, Jilin 130021, P. R. China Submission: October 30, 2019 Published: September 30, 2021 DOI: 10.31031/NACS.2021.06.000637 ISSN:2637-773XVolume6 Issue3

Prospects for the diagnosis and gene therapy of inherited retinal dystrophies caused by biallelic mutations in the RPE65 gene

Inherited retinal dystrophies (IRD) is an extensive group of genetically heterogeneous diseases with significant clinical polymorphism. With the development of gene therapy, a new era in the treatment of hereditary human diseases has opened. To date, clinical studies of a number of gene medications are performed the world over, including those intended for the treatment of hereditary eye diseases (Leber congenital amaurosis (LCA), retinitis pigmentosa, achromatopsia, Stargardt's disease, choroideremia, etc.). The varieties of two former conditions, specifically LCA type 2 and retinitis pigmentosa (RP) type 20 with biallelic mutations in the RPE65 gene belong to IRD. Epidemiological studies indicate the rarity of these diseases, which explains why IRD caused by biallelic mutations in the RPE65 gene are included into the list of rare (orphan) diseases of the Russian Ministry of Health. For these IRDs, a gene replacement therapy has been developed: voretigen neparvovek, which must only be applied once. Currently, the Medical Genetic Research Center and Helmholtz National Medical Research Center of Eye Diseases have identified a group of patients who meet the criteria for genetic therapy. In 2021, а specialized gene therapy center has been established at the Helmholtz Research Center, which was certified by the Ministry of Health. A group of leading experts in the field of inherited retinal diseases and medical genetics developed and approved at professional workshops a number of measures that promote the introduction into clinical practice of the voretigen neparvovek as a gene replacement therapy for the treatment of RPE65-related IRD in the Russian Federation.

20-year experience on prenatal diagnosis in a reference university medical genetics center in Turkey

Background/aimAlthough cutting edge procedures such as cell-free fetal DNA isolation from maternal blood are now available, invasive prenatal tests are still being used extensively for prenatal diagnosis. The study aims to evaluate the demographic data, indications, and cytogenetic results of 9297 results of patients who underwent prenatal invasive testing for genetic analysis that were referred for the last 20 years in a University Medical Genetics Center.Materials and methodsThe records of 8363 amniocenteses, 626 chorionic villus, and 308 cordocenteses samples were retrospectively evaluated and analyzed regarding referral reasons, indications and their cytogenetic results. The total numbers and the percentages of each group were recorded; Chi-square and logistic regression analyses were performed to give the statistical likelihood of different events. ResultsThe number of referrals decreased significantly after 2009. Risk of having trisomy 21 as well as trisomy 13 and 18 significantly increased in parallel with advanced maternal age. When the 21–25 age group was compared to the older age groups in terms of having a trisomy 21 pregnancy, the risk doubled in the 36–40, 5 times higher in 41–45 and 10-fold in 46–50 age groups. No significant linear correlation between maternal serum screening test results and trisomy 21 was found, however the difference between the pregnancies whom cut-off value above and below 1/250 in maternal serum screening test were significant.ConclusionThese data have provided useful information on the frequency of referrals to the reference genetics department, and the feasibility of genetic services. By reviewing the indications and their corresponding results, we can offer invaluable insights that will be useful in genetic counseling and also in the development of more effective genetic strategies.

The Results of a Prospective Cohort Study of the Effectiveness of the Algorithm for Monitoring Pregnancies in Patients from the Group of High Perinatal Risk to Reduce Perinatal Losses and Improve Neonatal Outcome

Prenatal prognosis is an important part of obstetric care, which aims to reduce fetal and neonatal losses. A differentiated approach to the management of different risk groups allows you to optimize existing approaches. The objective: сomparison of pregnancy results in the high perinatal risk group using the proposed monitoring algorithms and the traditional method of management in a prospective cohort study. Materials and methods. The prospective cohort study was conducted from 2016 to 2018 on the basis of the medical center LLC «Uniclinica», Medical Genetics Center «Genome», Clinic of Reproductive Genetics «Victoria», Kyiv City Maternity Hospital №2. 580 women were included in the final analysis. Exclusion criteria were: low risk (0–2) according to the adapted antenatal risk scale (Alberta perinatal health program), multiple pregnancy, critical malformations and chromosomal abnormalities of the fetus, lack of complete information about the outcome of pregnancy, lack of results of all intermediate clinical and laboratory surveys. Results. The introduction of a comprehensive differentiated approach has improved the diagnosis of late forms of growth retardation (OR 4,14 [1.42–12.09]; p=0,009), reduced the frequency of urgent cesarean sections (OR 1,61 [1,03–2,49]; p=0,046) and reduced perinatal mortality [1,09–21,3]; р=0,041) due to reduction of antenatal losses (OR 2,2 [1,06–4,378]; р=0,045). There was a significant increase in the frequency of planned cesarean sections (p<0,0001, without affecting the total number of operative deliveries) and statistically insignificant, but tendentiously clear shifts to the increase in the frequency of preterm birth between 34–37 weeks of pregnancy and intensive care unit. The latter observation can be explained by better diagnosis of threatening fetal conditions and an increase in the frequency of active obstetric tactics, which in turn affects the number of premature infants, the involvement of the neonatal service, and thus the intensification of the load on intensive. Conclusions. Adequate enhanced monitoring should combine ultrasound, cardiotocography, actography and laboratory techniques, each of which will have a clearly defined purpose in a combined approach to fetal assessment.

In memoriam of our colleagues and friends

The Department of General and Molecular Medical Genetics of St. Petersburg State Pediatric Medical University has existed for more than thirty years. Over these years, three outstanding scientists and clinical geneticists, our colleagues and members of the department, have passed away. Fundamental works of A.M. Polishchuk contributed to the study of radiation-induced chromosomal instability. One of the pioneers in the field of clinical cytogenetics in our country, A.M. Polishchuk was also at the origins of teaching genetics to future doctors. He was in the staff of the Department of Medical Genetics of St. Petersburg State Pediatric Medical University since its foundation in 1989, where his teaching experience was very appreciated. Having emigrated to Israel in the mid-1990s, A.M. Polishchuk continued his studies in laboratory genetics. The history of the development of genetics in Russia remained In the field of scientific interests of A.M. Polishchuk, until recent years. A.M. Polishchuk died in February 2020. Among the first members of the Department of Medical Genetics was also V.V. Krasilnikov. A student of the famous geneticist-neurologist E.A. Savelyeva-Vasilyeva, V.V. Krasilnikov became a prominent specialist in the field of clinical genetics, who spent more than three decades working at the Medical Genetic Center. An excellent diagnostician, he had a broad scientific outlook and deep knowledge in the study of microanomalies of development in hereditary pathology. After a long-lasting illness V.V. Krasilnikov died in 2012. V.G. Vakharlovsky was also a student of E.A. Savelyeva-Vasilyeva. The opus magnum of this outstanding clinician was the development of methods for pathogenetic therapy of the very grave hereditary diseases: WilsonKonovalov disease and spinal muscular atrophy. Having joined the team of the Department of Medical Genetics of the St. Petersburg State Pediatric Medical University in the 2000s, he brought into the educational process the practice of visiting a boarding home for mentally-handicapped children, introduced regular case studies. In 2010, with the Vakharlovskys death our collective suffered the big loss.