A founder mutation p.H701P identified as a major cause of SPG7 in Norway

作者：Rydning S L^*; Wedding I M; Koht J; Chawla M; Oye A M; Sheng Y; Vigeland M D; Selmer K K; Tallaksen C M E

来源：European Journal of Neurology, 2016, 23(4): 763-771.

DOI：10.1111/ene.12937

• founder mutation
• hereditary ataxia
• hereditary spastic paraplegia
• p.H701P
• spastic ataxia
• SPG7

Background and purposeSPG7 is one of the most common forms of autosomal recessive hereditary spastic paraplegia. The phenotype has been shown to be heterogeneous, varying from a complex spastic ataxia to pure spastic paraplegia or pure ataxia. The aim of this study was to clinically and genetically characterize patients with SPG7 in Norway.
MethodsSix Norwegian families with a clinical diagnosis of hereditary spastic paraplegia were diagnosed with SPG7 through Sanger sequencing and whole-exome sequencing. Haplotypes were established to identify a possible founder mutation. All patients were thoroughly examined and the clinical and molecular findings are described.
ResultsThe core phenotype was spastic paraparesis with ataxia, bladder disturbances and progressive external ophthalmoplegia. The variant p.H701P was identified in homozygous state in one family and in compound heterozygous state in three families. Haplotype analysis of seven surrounding single nucleotide polymorphisms supports that this variant resides on a founder haplotype. Four of the families were compound heterozygous for the previously well-described p.A510V variant.
ConclusionSPG7 is a common subgroup of hereditary spinocerebellar disorders in Norway. The broad phenotype in the Norwegian SPG7 population illustrates the challenges with the traditional dichotomous classification of hereditary spinocerebellar disorders into hereditary spastic paraplegia or hereditary ataxia. A Norwegian founder mutation p.H701P was identified in four out of six families, making it a major cause of SPG7 in Norway.

• 出版日期2016-4