Annals of neurology · 2006
Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis.
Клинический случайСравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Eymard-Pierre Eleonore, Yamanaka Koji, Haeussler Martin, Kress Wolfram, Gauthier-Barichard Fernande, Combes Patricia, Cleveland Don W, Boespflug-Tanguy Odile
Аннотация
OBJECTIVE: Recessive mutations in ALS2 (juvenile amyotrophic lateral sclerosis) are causative for early-onset upper motor neuron diseases, including infantile ascending hereditary spastic paralysis (IAHSP). The goal of this study is to identify novel disease-causing ALS2 mutations.
METHODS: Mutations in ALS2 were screened by direct sequencing of complementary DNA obtained from patients' lymphoblasts.
RESULTS: We report a novel ALS2 missense mutation in patients affected by IAHSP. This homozygous G669A mutation in exon 4 is predicted to result in a tyrosine substitution at cysteine 156 of the RCC1 (regulator of chromatin condensation)-like domain, encoding a putative guanine exchange factor for Ran guanosine triphosphatase, leading to a loss of ALS2 function due to instability of mutant protein.
INTERPRETATION: These results highlight the important role of the RCC1-like domain in ALS2 stability and function that is essential for upper motor neuron maintenance.
METHODS: Mutations in ALS2 were screened by direct sequencing of complementary DNA obtained from patients' lymphoblasts.
RESULTS: We report a novel ALS2 missense mutation in patients affected by IAHSP. This homozygous G669A mutation in exon 4 is predicted to result in a tyrosine substitution at cysteine 156 of the RCC1 (regulator of chromatin condensation)-like domain, encoding a putative guanine exchange factor for Ran guanosine triphosphatase, leading to a loss of ALS2 function due to instability of mutant protein.
INTERPRETATION: These results highlight the important role of the RCC1-like domain in ALS2 stability and function that is essential for upper motor neuron maintenance.