Ancient founder mutation in RUBCN: a second unrelated family confirms Salih ataxia (SCAR15)
| Autor: | Abdulmajeed AlDrees, Jumanah Al-Sufayan, Albandary Al-Bakheet, Salah A. Elmalik, Ibrahim A. Alorainy, Mohammed Zain Seidahmed, Dilek Colak, Namik Kaya, Ibrahim M. Ghozzi, Muddathir H. Hamad, Mustafa A. Salih |
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| Rok vydání: | 2020 |
| Předmět: |
Gait Ataxia
Male Ataxia Adolescent Autophagy-Related Proteins Case Report lcsh:RC346-429 Frameshift mutation 03 medical and health sciences 0302 clinical medicine Cerebellum Salih ataxia medicine Humans Spinocerebellar Ataxias Cognitive Dysfunction Child Frameshift Mutation Founder mutation Exome lcsh:Neurology. Diseases of the nervous system 030304 developmental biology Genetics 0303 health sciences Cerebellar ataxia business.industry SCAR15 Haplotype General Medicine medicine.disease Magnetic Resonance Imaging Mutation (genetic algorithm) Spinocerebellar ataxia RUBCN Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | BMC Neurology BMC Neurology, Vol 20, Iss 1, Pp 1-7 (2020) |
| ISSN: | 1471-2377 |
| DOI: | 10.1186/s12883-020-01761-w |
| Popis: | Background Homozygous frameshift mutation in RUBCN (KIAA0226), known to result in endolysosomal machinery defects, has previously been reported in a single Saudi family with autosomal recessive spinocerebellar ataxia (Salih ataxia, SCAR15, OMIM # 615705). The present report describes the clinical, neurophysiologic, neuroimaging, and genetic findings in a second unrelated Saudi family with two affected children harboring identical homozygous frameshift mutation in the gene. It also explores and documents an ancient founder cerebellar ataxia mutation in the Arabian Peninsula. Case presentation The present family has two affected males (aged 6.5 and 17 years) with unsteady gait apparent since learning to walk at 2.5 and 3 years, respectively. The younger patient showed gait ataxia and normal reflexes. The older patient had saccadic eye movement, dysarthria, mild upper and lower limb and gait ataxia (on tandem walking), and enhanced reflexes in the lower limbs. Cognitive abilities were mildly impaired in the younger sibling (IQ 67) and borderline in the older patient (IQ 72). Nerve conduction studies were normal in both patients. MRI was normal at 2.5 years in the younger sibling. Brain MRI showed normal cerebellar volume and folia in the older sibling at the age of 6 years, and revealed minimal superior vermian atrophy at the age of 16 years. Autozygome and exome analysis showed both affected have previously reported homoallelic mutation in RUBCN (NM_014687:exon18:c.2624delC:p.A875fs), whereas the parents are carriers. Autozygosity mapping focused on smallest haplotype on chromosome 3 and mutation age analysis revealed the mutation occurred approximately 1550 years ago spanning about 62 generations. Conclusions Our findings validate the slowly progressive phenotype of Salih ataxia (SCAR15, OMIM # 615705) by an additional family. Haplotype sharing attests to a common founder, an ancient RUBCN mutation in the Arab population. |
| Databáze: | OpenAIRE |
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