KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families
Autor: | Elena L. Dadali, T. V. Markova, V. A. Kadnikova, A. V. Polyakov, G. E. Rudenskaya, D. N. Khmelkova, D. S. Guseva, L. A. Bessonova, O. P. Ryzhkova |
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Rok vydání: | 2020 |
Předmět: |
Adult
Male Heterozygote Gene panel Adolescent Kinesins lcsh:RC346-429 Russia Young Adult 03 medical and health sciences symbols.namesake Phenotypic variability 0302 clinical medicine Intellectual Disability Spastic Humans Medicine Child Gene lcsh:Neurology. Diseases of the nervous system Exome sequencing KIF1A Paraplegia Genetics Sanger sequencing 0303 health sciences Massive parallel sequencing KIF1A gene business.industry Pure phenotype 030305 genetics & heredity High-Throughput Nucleotide Sequencing Pathogenic variants General Medicine Middle Aged Penetrance Phenotype Child Preschool Mutation symbols Female Additional features Neurology (clinical) business 030217 neurology & neurosurgery Research Article Autosomal dominant spastic paraplegia type 30 (SPG30) |
Zdroj: | BMC Neurology BMC Neurology, Vol 20, Iss 1, Pp 1-14 (2020) |
ISSN: | 1471-2377 |
Popis: | 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. |
Databáze: | OpenAIRE |
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