Premium
A Newly Identified Missense Mutation in FARS2 Causes Autosomal‐Recessive Spastic Paraplegia
Author(s) -
Yang Ying,
Liu Wei,
Fang Zhipeng,
Shi Juan,
Che Fengyu,
He Chunxia,
Yao Libo,
Wang Enduo,
Wu Yuanming
Publication year - 2016
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.22930
Subject(s) - missense mutation , hereditary spastic paraplegia , biology , mutation , genetics , exome sequencing , spasticity , gene , phenotype , medicine , physical therapy
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by spasticity of the lower limbs due to pyramidal tract dysfunction. Here, we report that a missense homozygous mutation c.424G>T (p.D142Y) in the FARS2 gene, which encodes a mitochondrial phenylalanyl tRNA synthetase (mtPheRS), causes HSP in a Chinese consanguineous family by using combination of homozygous mapping and whole‐exome sequencing. Immunohistochemical experiments were performed showing that the FARS2 protein was highly expressed in the Purkinje cells of rat cerebellum. The aminoacylation activity of mtPheRS was severely disrupted by the p.D142Y substitution in vitro not only in the first aminoacylation step but also in the last transfer step. Taken together, our results indicate that a missense mutation in FARS2 contributes to HSP, which has the clinical significance of the regulation of tRNA synthetases in human neurodegenerative diseases.