期刊
HUMAN MUTATION
卷 31, 期 4, 页码 E1251-E1260出版社
WILEY-BLACKWELL
DOI: 10.1002/humu.21205
关键词
FA2H; hereditary spastic paraplegia; mutation; SPG35; leukodystrophy
资金
- Newlife
- Bachmann-Strauss Foundation
- Medical Research Council (MRC)
- Brain Research Trust (BRT)
- Ataxia UK
- HM Sultan Qaboos
- Medical Research Council [G0600983] Funding Source: researchfish
- MRC [G0600983] Funding Source: UKRI
Hereditary spastic paraplegia (HSP) describes a heterogeneous group of inherited neurodegenerative disorders in which the cardinal pathological feature is upper motor neurone degeneration leading to progressive spasticity and weakness of the lower limbs. Using samples from a large Omani family we recently mapped a gene for a novel autosomal recessive form of HSP (SPG35) in which the spastic paraplegia was associated with intellectual disability and seizures. Magnetic resonance imaging of the brain of SPG35 patients showed white matter abnormalities suggestive of a leukodystrophy. Here we report homozygous mutations in the fatty acid 2-hydroxylase gene (FA2H) in the original family used to define the SPG35 locus (p.Arg235Cys) as well as in a previously unreported Pakistani family with a similar phenotype (p.Arg53_Ile58del). Measurement of enzyme activity in vitro revealed significantly reduced enzymatic function of FA2H associated with these mutations. These results demonstrate that mutations in FA2H are associated with SPG35, and that abnormal hydroxylation of myelin galactocerebroside lipid components can lead to a severe progressive phenotype, with a clinical presentation of complicated HSP and radiological features of leukodystrophy. (C) 2010 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据