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Distinct novel mutations affecting the same base in the NIPA1 gene cause autosomal dominant hereditary spastic paraplegia in two Chinese families
Author(s) -
Chen Suqin,
Song Chun,
Guo Hui,
Xu Pingyi,
Huang Weijun,
Zhou Yan,
Sun Jiandong,
Li CaiXia,
Du Yong,
Li Xunhua,
Liu Zhuolin,
Geng Deqin,
Maxwell Patrick H.,
Zhang Cheng,
Wang Yiming
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20126
Subject(s) - hereditary spastic paraplegia , biology , genetics , gene , locus (genetics) , exon , transmembrane domain , phenotype
Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized by lower‐limb spasticity, hyperreflexia, progressive spastic gait abnormalities, and an extensor‐plantar response. It is genetically very heterogeneous, with 28 Human Genome Organisation (HUGO)‐approved IDs in the database (last search: August 8, 2004). Following the identification of the SPG6 gene, NIPA1 , we have identified two novel mutations, c.316G>C and c.316G>A, in two independent Chinese families linked to the SPG6 locus. These two mutations would cause a p.G106R substitution, and cosegregated with the disease. Structural predictions suggest that p.G106 is located in the third transmembrane domain of the protein, and that the mutant p.G106R disrupts this structure, causing the intramembrane loop to descend into the cytoplasm. Our results identify two novel mutations responsible for HSP and suggest that c.316 of the NIPA1 gene may be a mutational hotspot. Hum Mutat 25:135–141, 2005. © 2005 Wiley‐Liss, Inc.