Molecular genetics of familial spastic paraplegia

遗传性痉挛性截瘫（HSP）是一组罕见的疾病，其特点是具有很大的临床和遗传异质性。迄今为止，9个常染色体显性HSP位点、3个x连锁HSP位点和4个常染色体隐性HSP位点已被鉴定。我们临床鉴定了13个日本常染色体隐性HSP家族，并进行了遗传连锁分析。13个科均为“复杂”型，表现为精神障碍和胼胝体薄。与8p12-q13和16qter位点的连锁被排除，而13个家族中有10个显示与15q13-15位点的连锁一致的标记数据。与第15染色体连锁的10个家系在D15S994和D15S659相邻的3cm区段的多点LOD评分均在9.00以上，其中D15S994 ~ D15S659端粒1.2 cM位置的多点LOD评分最高为9.68。我们已经表明，ARHSP与TCC，隐性痉挛性截瘫的一个亚型映射到染色体15q13-15。我们没有发现ARHSP与TCC和我们研究中使用的标记位点之间的任何连锁不平衡。由于在研究中标记位于0.5 cM间隔，因此需要使用更密集的标记来进一步研究连锁不平衡。

The hereditary spastic paraplegia (HSP) is a group of rare disorders that are characterized by great clinical and genetic heterogeneity. To date, nine loci for autosomal dominant HSP, three loci for X-linked HSP, and four loci for autosomal recessive HSP have been characterized. We have clinically characterized 13 Japanese autosomal recessive HSP families and performed genetic linkage analyzes. All the 13 families were classified as the "complicated" forms, which manifested with mental impairment and thin corpus callosum (TCC). Linkage to the 8p12-q13 and 16qter loci was excluded, while ten of the 13 families showed marker data consistent with linkage to 15q13-15. The multipoint LOD score of the 10 families linked to chromosome 15 was above 9.00 in the 3 cM segment flanked by D15S994 and D15S659, with a maximum multipoint LOD score of 9.68 at a position 1.2 cM telomeric from D15S994 to D15S659. We have shown that ARHSP with TCC, a subtype of recessive spastic paraplegia maps to chromosome 15q13-15. We did not detect any linkage disequilibrium between ARHSP with TCC and the marker loci used in our study. Since the markers were located at 0.5 cM intervals in the study, use of more densely placed markers will be required for further investigation on the linkage disequilibrium.