Rare Cause 5q SMA: Molecular Genetic and Clinical Analyses of Intragenic Subtle Variants in the SMN Locus.
| Title: | Rare Cause 5q SMA: Molecular Genetic and Clinical Analyses of Intragenic Subtle Variants in the SMN Locus. |
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| Authors: | Mikhalchuk K; Research Centre for Medical Genetics, Moscow, Russia.; Zabnenkova V; Research Centre for Medical Genetics, Moscow, Russia.; Braslavskaya S; Research Centre for Medical Genetics, Moscow, Russia.; Chukhrova A; Research Centre for Medical Genetics, Moscow, Russia.; Ryadninskaya N; Research Centre for Medical Genetics, Moscow, Russia.; Dadaly E; Research Centre for Medical Genetics, Moscow, Russia.; Rudenskaya G; Research Centre for Medical Genetics, Moscow, Russia.; Sharkova I; Research Centre for Medical Genetics, Moscow, Russia.; Anisimova I; Research Centre for Medical Genetics, Moscow, Russia.; Bessonova L; Research Centre for Medical Genetics, Moscow, Russia.; Mishina I; Research Centre for Medical Genetics, Moscow, Russia.; Repina S; Research Centre for Medical Genetics, Moscow, Russia.; Petukhova M; Research Centre for Medical Genetics, Moscow, Russia.; Sparber P; Research Centre for Medical Genetics, Moscow, Russia.; Kuchina A; Research Centre for Medical Genetics, Moscow, Russia.; Saushev D; Research Centre for Medical Genetics, Moscow, Russia.; Artemieva S; Russian Children Neuromuscular Center, Veltischev Clinical Pediatric Research Institute of Pirogov Russian National Research Medical University, Moscow, Russia.; Kurbatov S; Research Institute of Experimental Biology and Medicine, Voronezh State Medical University Named After N.N. Burdenko, Voronezh, Russia.; Saratov State Medical University, Saratov, Russia.; Kanivets I; Genomed LLC, Moscow, Russia.; FSBEI FPE RMACPE MOH Russia, Moscow, Russia.; Zarubina V; Morozov Children's City Clinical Hospital, Moscow, Russia.; Barykova D; State Budgetary Healthcare Institution Irkutsk Order of the Badge Regional Clinical Hospital, Irkutsk, Russia.; Lisakonova E; Docdeti LLC, Moscow, Russia.; Polyakov A; Research Centre for Medical Genetics, Moscow, Russia.; Shchagina O; Research Centre for Medical Genetics, Moscow, Russia. |
| Source: | Clinical genetics [Clin Genet] 2025 Jul; Vol. 108 (1), pp. 58-68. Date of Electronic Publication: 2025 Feb 04. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Munksgaard Country of Publication: Denmark NLM ID: 0253664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-0004 (Electronic) Linking ISSN: 00099163 NLM ISO Abbreviation: Clin Genet Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Copenhagen, Munksgaard. |
| MeSH Terms: | Survival of Motor Neuron 1 Protein*/genetics ; Muscular Atrophy, Spinal*/genetics ; Muscular Atrophy, Spinal*/diagnosis ; Muscular Atrophy, Spinal*/pathology ; Survival of Motor Neuron 2 Protein*/genetics ; Chromosomes, Human, Pair 5*/genetics; Humans ; Male ; Female ; Exons ; Child ; Child, Preschool ; Genetic Predisposition to Disease ; Alleles ; DNA Copy Number Variations |
| Abstract: | Spinal muscular atrophy 5q (5q SMA) is one of the most prevalent autosomal recessive disorders globally. The underlying cause of 5q SMA is attributed to variants in SMN1. Exon 7 of SMN1 is not detectable in major of probands with 5q SMA, and minor of probands have a combination of the deletion and an intragenic subtle variant in the second allele. From 1991 to 2023, DNA samples from 2796 probands representing unrelated families were analyzed at the Research Centre for Medical Genetics for the diagnosis of 5q SMA. The copy number of Exon 7 of SMN1 and SMN2 was determined for all probands by MLPA. Subsequently, direct automated Sanger sequencing was employed to perform intragenic subtle variant screenings in all 116 probands with one copy of Exon 7 of SMN1. The diagnosis of 5q SMA was confirmed in 1495 probands. Among the 41 probands with one copy of Exon 7 of SMN1 from the initial 116 tested, 24 intragenic subtle variants in SMN1/SMN2 were documented. The aim of this study was to identify and characterize intragenic subtle variants in SMN1 and analyze their relationship with clinical manifestations in probands with 5q SMA in the Russian cohort.; (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
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| Contributed Indexing: | Keywords: SMN1; 5q SMA; compound heterozygous; intragenic variant; mutation spectrum; spinal muscular atrophy; subtle variant |
| Substance Nomenclature: | 0 (Survival of Motor Neuron 1 Protein); 0 (SMN1 protein, human); 0 (Survival of Motor Neuron 2 Protein); 0 (SMN2 protein, human) |
| Entry Date(s): | Date Created: 20250205 Date Completed: 20250604 Latest Revision: 20250604 |
| Update Code: | 20260130 |
| DOI: | 10.1111/cge.14714 |
| PMID: | 39905579 |
| Database: | MEDLINE |
Journal Article