KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families.
| Title: | KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families. |
|---|---|
| Authors: | Rudenskaya GE; Federal State Budgetary Scientific Institution 'Research Centre for Medical Genetics' (RCMG), Moscow, Russia.; Kadnikova VA; Federal State Budgetary Scientific Institution 'Research Centre for Medical Genetics' (RCMG), Moscow, Russia. vkadnikova@gmail.com.; Ryzhkova OP; Federal State Budgetary Scientific Institution 'Research Centre for Medical Genetics' (RCMG), Moscow, Russia.; Bessonova LA; Federal State Budgetary Scientific Institution 'Research Centre for Medical Genetics' (RCMG), Moscow, Russia.; Dadali EL; Federal State Budgetary Scientific Institution 'Research Centre for Medical Genetics' (RCMG), Moscow, Russia.; Guseva DS; Federal State Budgetary Scientific Institution 'Research Centre for Medical Genetics' (RCMG), Moscow, Russia.; Markova TV; Federal State Budgetary Scientific Institution 'Research Centre for Medical Genetics' (RCMG), Moscow, Russia.; Khmelkova DN; 'Genomed' Ltd, Moscow, Russia.; Polyakov AV; Federal State Budgetary Scientific Institution 'Research Centre for Medical Genetics' (RCMG), Moscow, Russia. |
| Source: | BMC neurology [BMC Neurol] 2020 Aug 03; Vol. 20 (1), pp. 290. Date of Electronic Publication: 2020 Aug 03. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 100968555 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2377 (Electronic) Linking ISSN: 14712377 NLM ISO Abbreviation: BMC Neurol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, [2001- |
| MeSH Terms: | Kinesins/*genetics ; Paraplegia/*congenital; Intellectual Disability/genetics ; Paraplegia/genetics ; Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Middle Aged ; Mutation ; Phenotype ; Russia ; Young Adult |
| Abstract: | Background: Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population.; Methods: Clinical, genealogical and molecular methods were used. Molecular methods included massive parallel sequencing (MPS) of custom panel 'spastic paraplegias' with 62 target genes complemented by familial Sanger sequencing. One case was detected by the whole -exome sequencing.; Results: AD SPG30 was detected in 10 unrelated families, making it the 3rd (8.4%) most common SPG form in the cohort of 118 families. No AR SPG30 cases were detected. In total, 9 heterozygous KIF1A mutations were detected, with 4 novel and 5 known mutations. All the mutations were located within KIF1A motor domain. Six cases had pure phenotypes, of which 5 were familial, where 2 familial cases demonstrated incomplete penetrance, early onset and slow relatively benign SPG course. All 4 complicated cases were caused by novel mutations without familial history. The phenotypes varied from severe in two patients (e.g. lack of walking, pronounced mental retardation) to relatively mild non-disabling symptoms in two others.; Conclusion: AD SPG30 is one of the most common forms of SPG in Russia, the disorder has pronounced clinical variability while pure familial cases represent a significant part. |
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| Contributed Indexing: | Keywords: Additional features; Autosomal dominant spastic paraplegia type 30 (SPG30); Gene panel; KIF1A gene; Massive parallel sequencing; Pathogenic variants; Phenotypic variability; Pure phenotype |
| Substance Nomenclature: | 0 (KIF1A protein, human); EC 3.6.4.4 (Kinesins) |
| SCR Disease Name: | Spastic Paraplegia 30, Autosomal Recessive |
| Entry Date(s): | Date Created: 20200805 Date Completed: 20201109 Latest Revision: 20211204 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7398351 |
| DOI: | 10.1186/s12883-020-01872-4 |
| PMID: | 32746806 |
| Database: | MEDLINE |
Journal Article