Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, PR China.
Singapore Med J. 2013 May;54(5):251-4. doi: 10.11622/smedj.2013102.
Hereditary spastic paraplegia (HSP) belongs to a large, heterogeneous group of progressive neurodegenerative diseases characterised by progressive lower extremity weakness and spasticity, which is caused by developmental failure or degeneration of motor axons in the corticospinal tract. Classical genetic studies have identified at least 46 genetic loci responsible for HSP.
A genetic study was conducted on a four-generation Chinese family with autosomal dominant HSP. The SPAST gene was investigated using linkage analysis and direct sequencing. Findings were compared with unaffected family members and 50 normal, unaffected individuals who were matched for geographical ancestry.
We identified a novel 14-bp heterozygous deletion that induced a frameshift mutation in exon 15 of SPAST (SPG4). This mutation is predicted to have functional impact and found to cosegregate with the disease phenotype.
Our results have expanded the mutation spectrum of the SPAST gene. These findings could help clinicians provide prenatal diagnosis of affected foetuses in families with a known history of such neurodegenerative diseases.
遗传性痉挛性截瘫（HSP）属于一组大型、异质性的进行性神经退行性疾病，其特征是进行性下肢无力和痉挛，这是由皮质脊髓束中运动轴突的发育失败或变性引起的。经典的遗传研究已经确定了至少 46 个导致 HSP 的遗传位点。
对一个四代中国常染色体显性遗传性痉挛性截瘫家系进行了遗传研究。采用连锁分析和直接测序研究 SPAST 基因。将研究结果与未受影响的家族成员和 50 名地理亲缘关系匹配的正常、未受影响的个体进行比较。
我们发现了一个新的 14 个碱基对的杂合缺失，导致 SPAST（SPG4）外显子 15 的移码突变。该突变预计具有功能影响，并与疾病表型共分离。
我们的研究结果扩展了 SPAST 基因突变谱。这些发现有助于临床医生对有此类神经退行性疾病家族史的胎儿进行产前诊断。
