Genetic Research Center Research Articles

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.

Emerging Epidemiological Data on Rare Intellectual Disability Syndromes from Analyzing the Data of a Large Iranian Cohort.

Intellectual disability (ID) is a genetically heterogeneous condition, and so far, 1679 human genes have been identified for this phenotype. Countries with a high rate of parental consanguinity, such as Iran, provide an excellent opportunity to identify the remaining novel ID genes, especially those with an autosomal recessive (AR) mode of inheritance. This study aimed to investigate the most prevalent ID genes identified via next-generation sequencing (NGS) in a large ID cohort at the Genetics Research Center (GRC) of the University of Social Welfare and Rehabilitation Sciences. First, we surveyed the epidemiological data of 619 of 1295 families in our ID cohort, who referred to the Genetics Research Center from all over the country between 2004 and 2021 for genetic investigation via the NGS pipeline. We then compared our data with those of several prominent studies conducted in consanguineous countries. Data analysis, including cohort data extraction, categorization, and comparison, was performed using the R program version 4.1.2. We categorized the most common ID genes that were mutated in more than two families into 17 categories. The most common syndromic ID in our cohort was AP4 deficiency syndrome, and the most common non-syndromic autosomal recessive intellectual disability (ARID) gene was ASPM. We identified two unrelated families for the 36 ID genes. We found 14 genes in common between our cohort and the Arab and Pakistani groups, of which three genes (AP4M1, AP4S1, and ADGRG1) were repeated more than once. To date, there has been no comprehensive targeted NGS platform for the detection of ID genes in our country. Due to the large sample size of our study, our data may provide the initial step toward designing an indigenously targeted NGS platform for the diagnosis of ID, especially common ARID in our population.

Lilly launches a genetic medicine research center in Boston

Lilly launches a genetic medicine research center in Boston

Genetic etiology of hearing loss in Iran.

Hearing loss (HL) is an etiologically heterogeneous disorder thataffects around 5% of the world's population. There has been an exponential increase in the identification of genes and variants responsible for hereditary HL over recent years. Iran, a country located in the Middle East, has a high prevalence of consanguineous marriages, so heterogeneous diseases such as HL are more common. Comprehensive studies using different strategies from linkage analysis to next-generation sequencing, especially exome-sequencing, have achieved significant success in identifying possible pathogens in deaf Iranian families. About 12% of non-syndromic autosomal recessive HL genes investigated to date, were first identified in families from Iran. Variations of 56 genes have been observed in families with NSHL in Iran. Variants in GJB2, SLC26A4, MYO15A, MYO7A, CDH23, and TMC1 account for 16.5%, 16.25%, 13.5%, 9.35%, 6.9% and 4.92%, cases of NSHL, respectively. In summary, there are also different diagnostic rates between studies conducted in Iran. In the comprehensive investigations conducted by the Genetic Research Center of the University of Social Welfare and Rehabilitation Sciences over the past 20years, the overall diagnosis rate is about 80% while there are other studies with lower diagnostic rates which could reflect differences in project designs, sampling, and accuracy and validity of the methods used. Furthermore, there are several syndromic HHLs in Iran including, Waardenburg syndrome, BOR syndrome, Brown-Vialetto-Van Laere syndrome, Wolfram syndrome, among which Pendred and Usher syndromes are well-studied. These results are of importance for further investigation and elucidation of the molecular basis of HHL in Iran.

Management of biobanking for medical genetics research

Biobanking is one of the most important elements of the modern infrastructure for biomedical research. Organization of a biobank on the basis of the N. P. Bochkov Medical Genetics Research Center provides a centralized infrastructure for preparing biomaterial for research. Biobank has the format of a research equipment sharing center and works with two types of unique biomaterials from patients with genetic diseases: blood/blood components and vital cells of various tissue origin. The storage facility of the Biobank is equipped with low-temperature (-80° C) and cryostorage (-196° C) systems. Identification and search of samples is carried out using a bar-coding system and is implemented through the information interface of the biobank, which is integrated into the general database of patients at the Medical Genetics Research Center. Information on biomaterial samples is presented in periodically updated catalogs on the page of equipment sharing center “Biobank”. Biobank collection is available to internal and external users.

Identification of Mutations in GATA2 Gene in Adult Bengali Bangladeshi Acute Myeloid Leukemia (AML) Patients

AML is a malignant disease of the bone marrow in which hematopoietic precursors are arrested in an early stage of development due to genetic alterations in normal hematopoietic stem cells. Several genes are identified for the disease and GATA2 gene is one of the important genes among them because mutations of GATA2 gene suppress leukemogenesis. In a country like Bangladesh, genetic services are at an early stage of development or even not yet developed. There is no adequate reporting on GATA2 gene mutations in adult Bengali Bangladeshi AML patients. The aim of the study was to determine the mutations of GATA2 gene in AML patients in the adult Bengali Bangladeshi population. The present study was a cross-sectional type of descriptive study. The study was carried out in the Genetic Research Center (GRC) of the Department of Anatomy, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh during the period of January 2018 to December 2018. The study includes 50 adult Bengali Bangladeshi AML patients. Informed written consent was obtained from the participants. For identifying the mutations peripheral venous blood was obtained from each patient and sequencing was done using ABI Sanger Sequencer 3730. Research shows the mean age is 25±14.2 and average age group of adult AML patients of Bengali Bangladeshis is 18-29 years (54%), among them 31 (62%) and 19 (38%) were females and males respectively. GATA2 gene mutations were identified in 1 of the 50 AML patients and shows synonymous, frameshift and missense variant compared with the database of dbSNP. Identification of different variant with this small sample size emphasizes the importance of exploring the genetic makeup of adult Bengali Bangladeshi AML patients to develop a database for proper screening and genetic counseling of the disease.

Embryo/Fetus Doses from 18F-Fludeoxyglucose Radiopharmaceutical in Positron Emission Tomography/ Computed Tomography.

Aim:The embryo/fetus may be accidentally exposed to ionizing radiation. The aim of this study is to calculate embryo/fetus doses in pregnant women who underwent F-18 fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan.Materials and Methods:Between June 2015 and June 2021, 15 pregnant women underwent F-18 FDG PET/CT applied to the Genetic Research Center (GETAM). The OLINDA/EXM package program was used for internal radiation dosimetry according to the Medical Internal Radiation Dose scheme. FetDose V4 computer software was used to compute the embryo/fetus absorbed dose from CT scan.Results:The amount of the injected F-18 FDG activity to patients varied between 333 and 555 MBq. The mean embryo/fetal dose from F-18 FDG was 7.2 ± 2.8 mGy. In addition, the CT component dose to the embryo/fetus dose ranged from 8.5 to 16 mGy with a mean of 12.14 ± 2.05.Conclusions:The embryo/fetus dose from F-18 FDG PET/CT was <15 mGy, however, questioning the women's childbearing prior to scintigraphy is the first-line strategy to avoid accidental radiation exposure and stochastic risks.

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.

Morphology characterization of gembili (Dioscorea esculenta L.) Tanimbar, Maluku Province

Gembili (Dioscorea esculenta L.) is a tuber of the type (clan) Dioscorea as a 27 - 37% carbohydrate producer and has a nutritional composition that varies according to species. The research was conducted from May to December 2019 in Tanimbar Island Regency, Maluku. Using the method of observation and description. The morphological character of the five local accessions showed that the characters of the same plant species were singular and striking, namely the presence of roots on the tuber surface and the location of the roots on the tuber surface. There were spines on the tuber surface, and the weight of the tubers of the five accessions averaged 1.71-2, 72 kg higher than the highest collection at the Genetic Research and Development Center for Agricultural Biotechnology and Genetic Resources, namely accessions R 506 (Lokal Tanatoraja) and R 601 (Lokal Manukan) which only weighed 1,000 g. The five accessions of the Gembili plant have the potential to be developed as an alternative food.

GENE2D: A NoSQL Integrated Data Repository of Genetic Disorders Data.

There are few sources from which to obtain clinical and genetic data for use in research in Saudi Arabia. Numerous obstacles led to the difficulty of integrating these data from silos and scattered sources to provide standardized access to large data sets for patients with common health conditions. To this end, we sought to contribute to this area and offer a practical and easy-to-implement solution. In this paper, we aim to design and implement a “not only SQL” (NoSQL) based integration framework to generate an Integrated Data Repository of Genetic Disorders Data (GENE2D) to integrate data from various genetic clinics and research centers in Saudi Arabia and provide an easy-to-use query interface for researchers to conduct their studies on large datasets. The major components involved in the GENE2D architecture consists of the data sources, the integrated data repository (IDR) as a central database, and the application interface. The IDR uses a NoSQL document store via MongoDB (an open source document-oriented database program) as a backend database. The application interface called Query Builder provides multiple services for data retrieval from the database using a custom query to answer simple or complex research questions. The GENE2D system demonstrates its potential to help grow and develop a national genetic disorders database in Saudi Arabia.

G3DMS: Design and Implementation of a Data Management System for the Diagnosis of Genetic Disorders.

Current health information systems used in genetic research centers and clinics in the Kingdom of Saudi Arabia have failed to enable researchers and health care physicians to utilize genetic and clinical data in their research. In this paper, we aim to design and implement a Genetic Disorders Diagnosis Data Management System (G3DMS) to support clinicians in the process of diagnosing genetic diseases and conducting genetic studies. A case study was undertaken to analyze a health information system in Saudi to understand its design problems via a brainstorming method. We then used the Barker’s system design method and a prototype to validate our proposed system via usability testing. This research has resulted in the development of the G3DMS that comprises: electronic data-capture forms for data entry; a customized query builder to display and modify patient data as well as form research queries; a module that allows historical data to be uploaded in the form of bulk data using a template; export data options to Excel and JavaScript Object Notation (JSON) format; and authorization access for healthcare researchers and clinicians. The G3DMS was implemented in the Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Jeddah, KSA.

Big Data Approaches to Phenotyping Acute Ischemic Stroke Using Automated Lesion Segmentation of Multi-Center Magnetic Resonance Imaging Data.

Background and Purpose- We evaluated deep learning algorithms' segmentation of acute ischemic lesions on heterogeneous multi-center clinical diffusion-weighted magnetic resonance imaging (MRI) data sets and explored the potential role of this tool for phenotyping acute ischemic stroke. Methods- Ischemic stroke data sets from the MRI-GENIE (MRI-Genetics Interface Exploration) repository consisting of 12 international genetic research centers were retrospectively analyzed using an automated deep learning segmentation algorithm consisting of an ensemble of 3-dimensional convolutional neural networks. Three ensembles were trained using data from the following: (1) 267 patients from an independent single-center cohort, (2) 267 patients from MRI-GENIE, and (3) mixture of (1) and (2). The algorithms' performances were compared against manual outlines from a separate 383 patient subset from MRI-GENIE. Univariable and multivariable logistic regression with respect to demographics, stroke subtypes, and vascular risk factors were performed to identify phenotypes associated with large acute diffusion-weighted MRI volumes and greater stroke severity in 2770 MRI-GENIE patients. Stroke topography was investigated. Results- The ensemble consisting of a mixture of MRI-GENIE and single-center convolutional neural networks performed best. Subset analysis comparing automated and manual lesion volumes in 383 patients found excellent correlation (ρ=0.92; P<0.0001). Median (interquartile range) diffusion-weighted MRI lesion volumes from 2770 patients were 3.7 cm3 (0.9-16.6 cm3). Patients with small artery occlusion stroke subtype had smaller lesion volumes ( P<0.0001) and different topography compared with other stroke subtypes. Conclusions- Automated accurate clinical diffusion-weighted MRI lesion segmentation using deep learning algorithms trained with multi-center and diverse data is feasible. Both lesion volume and topography can provide insight into stroke subtypes with sufficient sample size from big heterogeneous multi-center clinical imaging phenotype data sets.

ДНК-диагностика Х-сцепленной хронической гранулематозной болезни

Хроническая гранулематозная болезнь (ХГБ) - наследственное заболевание, относящееся к группе первичных иммунодефицитов с нарушением функции фагоцитоза. Наиболее частой является Х-сцепленная форма ХГБ, которая развивается в результате молекулярного дефекта, возникающего в гене CYBB. В статье представлены результаты молекулярной диагностики Х-сцепленной ХГБ у пациентов из разных регионов России в лаборатории ДНК-диагностики Медико-генетического научного центра. Chronic granulomatous disease (CGD) is a hereditary disease belonging to the group of primary immunodeficiencies with impaired phagocytosis function. The most frequent is the X-linked form of CGB, which develops as a result of a molecular defect arising in the CYBB gene. The article presents the results accumulated in the Laboratory of DNA Diagnostics of the Medical Genetic Research Center during the molecular diagnosis of X-linked CGD in patients from different regions of Russia.

Glycogenosis type IX in a 9-year-old child

Since the age of 1 year, a child presented with hypoglycemic conditions accompanied by ketosis as well as periodic hyperglycemia, for which reason he was hospitalized to the Pediatric Endocrinology Department of the Mirotvortsev Saratov Clinical Hospital. At the hospital, the child underwent a comprehensive examination that excluded diseases such as hyperinsulinism and diabetes mellitus. In the Laboratory of Hereditary Diseases of Metabolism of the Medical Genetics Research Center, a hemizygotic mutation in the PHKA2 gene (glycogenosis type IX) was detected. The mother was also detected with the heterozygous mutation c.226G&gt;A (p.E76K in the PHKA2 gene). Based on the results of the genetic examination of the child and mother, the patient was finally diagnosed with glycogenosis type IX. The patient was put on an individualized protein diet avoiding edible sugar and fatty foods; corn starch (30 g every 6 h and overnight) was recommended. Strict adherence to the diet resulted in less frequent seizures and decreased severity of episodes.

Corrigendum

Aquaculture ResearchVolume 48, Issue 6 p. 3284-3284 CorrigendumFree Access Corrigendum This article corrects the following: Temporal expression analyses of pancreatic and gastric digestive enzymes during early development of the olive flounder (Paralichthys olivaceus) Young Mee Lee, Jeong-Ho Lee, Jae Koo Noh, Hyun Chul Kim, Choul-Ji Park, Jong-Won Park, Gyeong Eon Noh, Kyung-Kil Kim, Volume 48Issue 3Aquaculture Research pages: 979-989 First Published online: November 14, 2015 First published: 08 May 2017 https://doi.org/10.1111/are.13363AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat In Aquaculture Research 48:3, an article by Lee et al. (2017) entitled, “Temporal expression analyses of pancreatic and gastric digestive enzymes during early development of the olive flounder (Paralichthys olivaceus)” (pages 979–989), all the authors have agreed to change the corresponding author from Jae Koo Noh to Jeong-Ho Lee during peer review stage without the change being properly communicated. The correct authors and their affiliations are as follows: Young Mee Lee, Jeong-Ho Lee, Jae Koo Noh, Hyun Chul Kim, Choul-Ji Park, Jong-Won Park, Gyeong Eon Noh & Kyung-Kil Kim Genetics and Breeding Research Center, National Institute of Fisheries Science (NIFS), Geoje, Korea Correspondence: J-H Lee, Genetics and Breeding Research Center, National Institute of Fisheries Science (NIFS), Geoje 53334, Korea. E-mail: jhlee7124@korea.kr The authors apologize for this error. Reference Lee, Y. M., Lee, J.-H., Noh, J. K., Kim, H. C., Park, C.-J., Park, J.-W., Noh, G. E., Kim, K.-K. (2017). Temporal expression analyses of pancreatic and gastric digestive enzymes during early development of the olive flounder (Paralichthys olivaceus). Aquaculture Research, 48, 978– 989. Volume48, Issue6June 2017Pages 3284-3284 ReferencesRelatedInformation

The adipocyte clock controls brown adipogenesis via TGF/ BMP signaling pathway

The adipocyte clock controls brown adipogenesis via TGF-β/BMP signaling pathway Deokhwa Nam, Bingyan Guo, Somik Chatterjee, Miao-Hsueh Chen, David Nelson, Vijay K. Yechoor, Ke Ma* Center for Diabetes Research, Department of Medicine, The Methodist Hospital Research Institute, Houston, TX, 77030 Department of Cardiovascular Medicine, Second Affiliated Hospital, Hebei Medical University, Shijiazhuang, 050017, Hebei, China. Department of Pediatrics, Children’s Nutrition Research Center, Department of Molecular and Human Genetics, Diabetes and Endocrinology Research Center, Department of Medicine, Baylor College of Medicine, Houston, TX, 77030

Agreement between TOAST and CCS ischemic stroke classification: the NINDS SiGN study.

The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems. Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems. The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; κ = 0.59, 95% confidence interval [CI] 0.58-0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (κ = 0.71, 95% CI 0.69-0.73) and lowest for small-artery occlusion (κ = 0.56, 95% CI 0.54-0.58). Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner.

Stroke Genetics Network (SiGN) study: design and rationale for a genome-wide association study of ischemic stroke subtypes.

Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10,296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14,549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research-generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived. The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.

Comparative studies of vertebrate endothelin-converting enzyme-like 1 genes and proteins

Comparative studies of vertebrate endothelin-converting enzyme-like 1 genes and proteins Roger S Holmes,1,2 Laura A Cox11Department of Genetics and Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA; 2Eskitis Institute for Cell and Molecular Therapies and School of Biomolecular and Physical Sciences, Griffith University, Nathan, Queensland, AustraliaAbstract: Endothelin-converting enzyme-like 1 (ECEL1) is a member of the M13 family of neutral endopeptidases which play an essential role in the neural regulation of vertebrate respiration. Genetic deficiency of this protein results in respiratory failure soon after birth. Comparative ECEL1 amino acid sequences and structures and ECEL1 gene locations were examined using data from several vertebrate genome projects. Vertebrate ECEL1 sequences shared 66%&ndash;99% identity as compared with 30%&ndash;63% sequence identities with other M13-like family members, ECE1, ECE2, and NEP (neprilysin or MME). Three N-glycosylation sites were conserved among most vertebrate ECEL1 proteins examined. Sequence alignments, conserved key amino acid residues, and predicted secondary and tertiary structures were also studied, including cytoplasmic, transmembrane, and luminal sequences and active site residues. Vertebrate ECEL1 genes usually contained 18 exons and 17 coding exons on the negative strand. Exons 1 and 2 of the human ECEL1 gene contained 5&#39;-untranslated (5&#39;-UTR) regions, a large CpG island (CpG256), and several transcription factor binding sites which may contribute to the high levels of gene expression previously reported in neural tissues. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate ECEL1 gene with six other vertebrate neutral endopeptidase M13 family genes. These suggested that ECEL1 originated in an ancestral vertebrate genome from a duplication event in an ancestral neutral endopeptidase M13-like gene.Keywords: vertebrates, amino acid sequence, ECEL1, ECE1, ECE2, KELL, NEP, NEPL1, PHEX, evolution

The spectrum of CLCN1 gene mutations in patients with nondystrophic Thomsen’s and Becker’s myotonias

Thomsen's and Becker's diseases are the most prevalent nondystrophic myotonias. Their frequency varies, according to different sources, from 1 : 100 000 to 1 : 10 000. Thomsen's myotonia is autosomal dominant, and Becker's myotonia is autosomal recessive. Both diseases result from mutations of the CLCN1 gene encoding chloride ion channels of skeletal muscles. Molecular genetic analysis of the CLCN1 gene has been performed in patients with diagnoses of nondystrophic Thomsen's and Becker's myotonias living in the Russian Federation. A sample of 79 unrelated probands with nondystrophic Thomsen's and Becker's myotonias and 44 their relatives has been formed in the Laboratory of DNA Diagnosis of the Medical Genetic Research Center of the Russian Academy of Medical Sciences. Forty CLCN1 gene mutations have been found in a total of 118 chromosomes of 66 probands, including 21 familial and 45 sporadic cases. About half the mutations detected (45%) have been found for the first time; they are not described in the SNP database (ncbi.nlm.nih.gov). The following mutations (substitutions) have been detected in more than one chromosome, accounting for a total of 59.3% of chromosomes with mutations: Glyl90Ser (5.9%), c.1437-1450del14 (9.3%), Ala493Glu (5.1%), Thr550Met (3.4%), Tyr686Stop (5.1%), and Arg894Stop (30.5%).