Schlang Katharina J, Arning Larissa, Epplen Joerg T, Stemmler Susanne
Department of Human Genetics, Ruhr-University, 44801 Bochum, Germany.
BMC Med Genet. 2008 Jul 21;9:71. doi: 10.1186/1471-2350-9-71.
Mutations in the SPG4 gene (spastin) and in the SPG3A gene (atlastin) account for the majority of 'pure' autosomal dominant form of hereditary spastic paraplegia (HSP). Recently, mutations in the REEP1 gene were identified to cause autosomal dominant HSP type SPG31. The purpose of this study was to determine the prevalence of REEP1 mutations in a cohort of 162 unrelated Caucasian index patients with 'pure' HSP and a positive family history (at least two persons per family presented symptoms).
162 patients were screened for mutations by, both, DHPLC and direct sequencing.
Ten mutations were identified in the REEP1 gene, these included eight novel mutations comprising small insertions/deletions causing frame shifts and subsequently premature stop codons, one nonsense mutation and one splice site mutation as well as two missense mutations. Both missense mutations and the splice site mutation were not identified in 170 control subjects.
In our HSP cohort we found pathogenic mutations in 4.3% of cases with autosomal dominant inheritance. Our results confirm the previously observed mutation range of 3% to 6.5%, respectively, and they widen the spectrum of REEP1 mutations.
SPG4基因（痉挛蛋白）和SPG3A基因（atlastin）的突变是遗传性痉挛性截瘫（HSP）“纯”常染色体显性遗传形式的主要原因。最近，已确定REEP1基因的突变可导致常染色体显性遗传的SPG31型HSP。本研究的目的是确定162例无亲缘关系的具有“纯”HSP且家族史阳性（每个家族至少有两人出现症状）的白种人索引患者队列中REEP1突变的患病率。
通过变性高效液相色谱（DHPLC）和直接测序对162例患者进行突变筛查。
在REEP1基因中鉴定出10种突变，其中包括8种新突变，包括导致移码并随后产生过早终止密码子的小插入/缺失、1种无义突变和1种剪接位点突变以及2种错义突变。170名对照受试者中未发现错义突变和剪接位点突变。
在我们的HSP队列中，我们在4.3%的常染色体显性遗传病例中发现了致病突变。我们的结果证实了之前观察到的分别为3%至6.5%的突变范围，并且拓宽了REEP1突变谱。
