Schüle R, Schlipf N, Synofzik M, Klebe S, Klimpe S, Hehr U, Winner B, Lindig T, Dotzer A, Riess O, Winkler J, Schöls L, Bauer P
Department of Neurology, University of Tübingen, Tübingen, Germany.
J Neurol Neurosurg Psychiatry. 2009 Dec;80(12):1402-4. doi: 10.1136/jnnp.2008.167528.
Hereditary spastic paraplegias (HSP) are clinically and genetically highly heterogeneous. Recently, two novel genes, SPG11 (spatacsin) and SPG15 (spastizin), associated with autosomal recessive HSP, were identified. Clinically, both are characterised by complicated HSP and a rather similar phenotype consisting of early onset spastic paraplegia, cognitive deficits, thin corpus callosum (TCC), peripheral neuropathy and mild cerebellar ataxia.
To compare the frequency of SPG11 and SPG15 in patients with early onset complicated HSP and to further characterise the phenotype of SPG11 and SPG15.
A sample of 36 index patients with early onset complicated HSP and a family history compatible with autosomal recessive inheritance was collected and screened for mutations in SPG11 and SPG15. Overall frequency of SPG11 was 14% (5/36) but was considerably higher in patients with TCC (42%). One patient with mental retardation and thinning of the corpus callosum was compound heterozygous for two novel SPG15 mutations. Additionally, several new polymorphisms and sequence variants of unknown significance have been identified in the SPG15 gene.
TCC seems to be the best phenotypic predictor for SPG11 as well as SPG15. No clinical features could discriminate between SPG11 and SPG15. Therefore, priority of genetic testing should be driven by mutation frequency that appears to be substantially higher in SPG11 than in SPG15.
遗传性痉挛性截瘫(HSP)在临床和遗传方面具有高度异质性。最近,发现了两个与常染色体隐性遗传HSP相关的新基因,即SPG11(spatacsin)和SPG15(spastizin)。临床上,两者均表现为复杂型HSP,且具有相当相似的表型,包括早发性痉挛性截瘫、认知缺陷、胼胝体变薄(TCC)、周围神经病变和轻度小脑共济失调。
比较早发性复杂型HSP患者中SPG11和SPG15的发生率,并进一步明确SPG11和SPG15的表型。
收集了36例早发性复杂型HSP且家族史符合常染色体隐性遗传的索引患者样本,对其进行SPG11和SPG15突变筛查。SPG11的总体发生率为14%(5/36),但在有TCC的患者中发生率显著更高(42%)。1例患有智力发育迟缓且胼胝体变薄的患者为两个新的SPG15突变的复合杂合子。此外,在SPG15基因中还发现了几个新的多态性和意义不明的序列变异。
TCC似乎是SPG11和SPG15最佳的表型预测指标。没有临床特征能够区分SPG11和SPG15。因此,基因检测的优先级应由突变频率决定,SPG11的突变频率似乎显著高于SPG15。