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. Ann Neurol 2006;59:976-980.
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. Ann Neurol 2006;59:976-980.
Authors: Chen Lai; Chengsong Xie; Stefanie G McCormack; Hsueh-Cheng Chiang; Marta K Michalak; Xian Lin; Jayanth Chandran; Hoon Shim; Mika Shimoji; Mark R Cookson; Richard L Huganir; Jeffrey D Rothstein; Donald L Price; Philip C Wong; Lee J Martin; J Julius Zhu; Huaibin Cai Journal: J Neurosci Date: 2006-11-08 Impact factor: 6.167
Authors: Mahdi Ghani; Anthony E Lang; Lorne Zinman; Benedetta Nacmias; Sandro Sorbi; Valentina Bessi; Andrea Tedde; Maria Carmela Tartaglia; Ezequiel I Surace; Christine Sato; Danielle Moreno; Zhengrui Xi; Rachel Hung; Mike A Nalls; Andrew Singleton; Peter St George-Hyslop; Ekaterina Rogaeva Journal: Neurobiol Aging Date: 2014-08-01 Impact factor: 4.673