Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion
| Autor: | Yuishin Izumi, Nozomu Sato, Ludger Schöls, Yasushi Kita, Alain Vighetto, Alexis Brice, Masato Obayashi, Thomas Illig, Virginie Desestret, Thomas Klopstock, Giovanni Stevanin, Alexandra Durr, Kinya Ishikawa, Matthis Synofzik, Marie-Lorraine Monin, Johanna Huttenlocher, Charles Duyckaerts, Nathalie Streichenberger, Hidehiro Mizusawa, Christelle Tesson, H-Erich Wichmann |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
pathology [Spinocerebellar Ataxias] DNA Mutational Analysis Neurogenetics NOP56 protein human Nerve Tissue Proteins Neuropathology Biology pathology [Brain] medicine Humans Spinocerebellar Ataxias Neuroepidemiology SCA36 protein human ddc:610 genetics [Spinocerebellar Ataxias] Allele genetics [Nerve Tissue Proteins] Alleles Genetics Aged 80 and over pathology [Atrophy] Cerebellar ataxia Haplotype Brain Nuclear Proteins genetics [Nuclear Proteins] medicine.disease Introns Pedigree Psychiatry and Mental health Haplotypes Spinocerebellar ataxia Surgery Female Neurology (clinical) medicine.symptom Atrophy Trinucleotide repeat expansion Trinucleotide Repeat Expansion genetics [Atrophy] |
| Zdroj: | Journal of neurology, neurosurgery, and psychiatry 86(9), 986-995 (2014). doi:10.1136/jnnp-2014-309153 |
| ISSN: | 1468-330X |
| Popis: | Objective Spinocerebellar ataxia 36 (SCA36) is an autosomal-dominant neurodegenerative disorder caused by a large (>650) hexanucleotide GGCCTG repeat expansion in the first intron of the NOP56 gene. The aim of this study is to clarify the prevalence, clinical and genetic features of SCA36. Methods The expansion was tested in 676 unrelated SCA index cases and 727 controls from France, Germany and Japan. Clinical and neuropathological features were investigated in available family members. Results Normal alleles ranged between 5 and 14 hexanucleotide repeats. Expansions were detected in 12 families in France (prevalence: 1.9% of all French SCAs) including one family each with Spanish, Portuguese or Chinese ancestry, in five families in Japan (1.5% of all Japanese SCAs), but were absent in German patients. All the 17 SCA36 families shared one common haplotype for a 7.5 kb pairs region flanking the expansion. While 27 individuals had typically long expansions, three affected individuals harboured small hexanucleotide expansions of 25, 30 and 31 hexanucleotide repeat-units, demonstrating that such a small expansion could cause the disease. All patients showed slowly progressive cerebellar ataxia frequently accompanied by hearing and cognitive impairments, tremor, ptosis and reduced vibration sense, with the age at onset ranging between 39 and 65 years, and clinical features were indistinguishable between individuals with short and typically long expansions. Neuropathology in a presymptomatic case disclosed that Purkinje cells and hypoglossal neurons are affected. Conclusions SCA36 is rare with a worldwide distribution. It can be caused by a short GGCCTG expansion and associates various extracerebellar symptoms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|