Background: Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present. At least 22 genetic loc...Background: Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present. At least 22 genetic loci have been linked to HSP, 8 of which are autosomal recessive (ARHSP). HSP complicated with the presence of thin corpus callosum (HSP-TCC) is a common subtype of HSP. One genetic locus has been identified on chromosome 15q13-q15 (SPG11) for HSP-TCC, but some HSP-TCC families have not been linked to this locus. Methods: The authors characterized two families clinically and radiologically and performed a genome-wide scan and linkage analysis. Results: The two families had complicated ARHSP. The affected individuals in Family A had thin corpus callosum and mental retardation, whereas in Family B two of three affected individuals had epilepsy. In both families linkage analysis identified a locus on chromosome 8 between markers D8S1820 and D8S532 with the highest combined lod score of 7.077 at marker D8S505. This 9 cM interval located on 8p12-p11.21 represents a new locus for ARHSP-TCC. Neuregulin and KIF13B genes, located within this interval, are interesting functional candidate genes for this HSP form. Conclusion: Two consanguineous families with complicated autosomal recessive hereditary spastic paraplegia were clinically characterized and genetically mapped to a new locus on 8p12-p11.21.展开更多
目的:通过对胶原蛋白Ⅳ型α5链(collagen type Ⅳα 5 chain,COL4A5)基因进行分析,为1例X-连锁性遗传性Alport综合征家系的分子诊断和遗传咨询提供依据。探讨Alport综合征COL4A5基因移码突变谱及临床表型。方法:应用全外显子组测序技术...目的:通过对胶原蛋白Ⅳ型α5链(collagen type Ⅳα 5 chain,COL4A5)基因进行分析,为1例X-连锁性遗传性Alport综合征家系的分子诊断和遗传咨询提供依据。探讨Alport综合征COL4A5基因移码突变谱及临床表型。方法:应用全外显子组测序技术进行基因检测,应用Sanger测序法对候选致病变异进行验证。结果:病人肾损害渐进展,出现肉眼血尿、肾病综合征,抗感染治疗后蛋白尿及肉眼血尿可缓解。先证者肾脏病理活检:病理表现为基底膜厚薄不一,致密层增厚,部分呈撕裂状和蛛网状。高通量测序和一代测序结果均提示病人COL4A5基因49号外显子存在c.4518_c.4519 insC(p.Gln1507Profs*14)的杂合变异;病人父母均不携带该变异。结论:首次报道了COL4A5基因该位点的新生变异为病人的发病原因,丰富了COL4A5基因变异谱,为该X-连锁性遗传性肾炎家系的分子诊断及产前诊断提供了依据;对指导家族中母亲及女儿再生育,通过产前基因诊断或胚胎植入前遗传学诊断技术,阻断该疾病有重要意义。展开更多
文摘Background: Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present. At least 22 genetic loci have been linked to HSP, 8 of which are autosomal recessive (ARHSP). HSP complicated with the presence of thin corpus callosum (HSP-TCC) is a common subtype of HSP. One genetic locus has been identified on chromosome 15q13-q15 (SPG11) for HSP-TCC, but some HSP-TCC families have not been linked to this locus. Methods: The authors characterized two families clinically and radiologically and performed a genome-wide scan and linkage analysis. Results: The two families had complicated ARHSP. The affected individuals in Family A had thin corpus callosum and mental retardation, whereas in Family B two of three affected individuals had epilepsy. In both families linkage analysis identified a locus on chromosome 8 between markers D8S1820 and D8S532 with the highest combined lod score of 7.077 at marker D8S505. This 9 cM interval located on 8p12-p11.21 represents a new locus for ARHSP-TCC. Neuregulin and KIF13B genes, located within this interval, are interesting functional candidate genes for this HSP form. Conclusion: Two consanguineous families with complicated autosomal recessive hereditary spastic paraplegia were clinically characterized and genetically mapped to a new locus on 8p12-p11.21.
