Jana Zídková, Barbora Lauerová, Lívie Mensová, Tereza Kramářová, Johana Kopčilová, Kamila Réblová, Magdaléna Soukup Vodičková, Martina Hujňáková, Jana Haberlová, Marie Rohlenová, Radim Mazanec, Jana Šoukalová, Renata Gaillyová, Emílie Vyhnálková, Miroslava Balaščaková, Pavlína Danhofer, Lenka Juříková, Dagmar Grečmalová, Andrea Gřegořová, Pavlína Plevová, Martina Langová, Tomáš Honzík, Martin Magner, Martina Klincová, Pavla Solařová, Mária Šenkeříková, Lenka Fajkusová
{"title":"捷克先天性肌病患者的遗传和结构变异。","authors":"Jana Zídková, Barbora Lauerová, Lívie Mensová, Tereza Kramářová, Johana Kopčilová, Kamila Réblová, Magdaléna Soukup Vodičková, Martina Hujňáková, Jana Haberlová, Marie Rohlenová, Radim Mazanec, Jana Šoukalová, Renata Gaillyová, Emílie Vyhnálková, Miroslava Balaščaková, Pavlína Danhofer, Lenka Juříková, Dagmar Grečmalová, Andrea Gřegořová, Pavlína Plevová, Martina Langová, Tomáš Honzík, Martin Magner, Martina Klincová, Pavla Solařová, Mária Šenkeříková, Lenka Fajkusová","doi":"10.1111/cge.14782","DOIUrl":null,"url":null,"abstract":"<p><p>Congenital myopathies (CMs) are a heterogeneous group of genetic muscle disorders characterized by hypotonia and muscle weakness, with pathogenic variants identified in at least 41 genes and inheritance patterns including autosomal dominant (AD), recessive (AR), and X-linked (XL). We present 79 unrelated patients with genetically confirmed CM using next-generation sequencing (NGS). A total of 113 mutant alleles carrying 97 different variants with a presumed pathogenic effect were identified. According to the HGMD database, 54 of these variants have been reported exclusively in the Czech CM population to date. All but five variants were small-scale. Large gene deletions were identified in the MTM1, NEB, and RYR1 genes. Sequencing of breakpoint junctions in the identified NEB and RYR1 deletions provided insights into the upstream mechanisms leading to genomic instability and resulting in structural variations. We present the family with dominant inheritance of the NEB deletion of exons 19-78. We assume that our family represents another reported case of a dominant mutation in the NEB gene. Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic and Structural Variations in Czech Patients With Congenital Myopathies.\",\"authors\":\"Jana Zídková, Barbora Lauerová, Lívie Mensová, Tereza Kramářová, Johana Kopčilová, Kamila Réblová, Magdaléna Soukup Vodičková, Martina Hujňáková, Jana Haberlová, Marie Rohlenová, Radim Mazanec, Jana Šoukalová, Renata Gaillyová, Emílie Vyhnálková, Miroslava Balaščaková, Pavlína Danhofer, Lenka Juříková, Dagmar Grečmalová, Andrea Gřegořová, Pavlína Plevová, Martina Langová, Tomáš Honzík, Martin Magner, Martina Klincová, Pavla Solařová, Mária Šenkeříková, Lenka Fajkusová\",\"doi\":\"10.1111/cge.14782\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Congenital myopathies (CMs) are a heterogeneous group of genetic muscle disorders characterized by hypotonia and muscle weakness, with pathogenic variants identified in at least 41 genes and inheritance patterns including autosomal dominant (AD), recessive (AR), and X-linked (XL). We present 79 unrelated patients with genetically confirmed CM using next-generation sequencing (NGS). A total of 113 mutant alleles carrying 97 different variants with a presumed pathogenic effect were identified. According to the HGMD database, 54 of these variants have been reported exclusively in the Czech CM population to date. All but five variants were small-scale. Large gene deletions were identified in the MTM1, NEB, and RYR1 genes. Sequencing of breakpoint junctions in the identified NEB and RYR1 deletions provided insights into the upstream mechanisms leading to genomic instability and resulting in structural variations. We present the family with dominant inheritance of the NEB deletion of exons 19-78. We assume that our family represents another reported case of a dominant mutation in the NEB gene. 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Genetic and Structural Variations in Czech Patients With Congenital Myopathies.
Congenital myopathies (CMs) are a heterogeneous group of genetic muscle disorders characterized by hypotonia and muscle weakness, with pathogenic variants identified in at least 41 genes and inheritance patterns including autosomal dominant (AD), recessive (AR), and X-linked (XL). We present 79 unrelated patients with genetically confirmed CM using next-generation sequencing (NGS). A total of 113 mutant alleles carrying 97 different variants with a presumed pathogenic effect were identified. According to the HGMD database, 54 of these variants have been reported exclusively in the Czech CM population to date. All but five variants were small-scale. Large gene deletions were identified in the MTM1, NEB, and RYR1 genes. Sequencing of breakpoint junctions in the identified NEB and RYR1 deletions provided insights into the upstream mechanisms leading to genomic instability and resulting in structural variations. We present the family with dominant inheritance of the NEB deletion of exons 19-78. We assume that our family represents another reported case of a dominant mutation in the NEB gene. Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease