一个痉挛性截瘫31型家系REEP1基因的变异分析

Deletional variant of REEP1 gene in a pedigree affected with spastic paraplegia type 31

目的 对1个遗传性痉挛性截瘫31型家系患者的REEP1基因拷贝数变异进行分析,探讨可能的分子遗传学发病机制.方法 在遗传性痉挛性截瘫相关基因组外显子区域定制罗氏NimbleGen捕获探针进行目标基因全外显子捕获,进行同组荧光定量PCR.应用CytoScan HD芯片行染色体微阵列分析.结果 先证者及其父亲、祖父2号染色体85 942 693-86 842 693碱基存在缺失,缺失片段长度约900 kb.该区域涉及与遗传性痉挛性截瘫31型明确相关的REEP1基因.先证者及其父亲、祖父目标范围存在杂合缺失,临床表型正常的母亲未检测到该突变.结论 拷贝数变异所致REEP1基因缺失变异可能是引起本家系发病的原因.

Objective To detect pathogenic variation in a pedigree affected with hereditary spastic paraplegia type 31 and explore its molecular pathogenesis.Methods Customized Roche NimbleGen capture probes were used to capture all exons of the target genes in relation with hereditary spastic paraplegia.The DNA samples were also assayed with fluorescent quantitative PCR as well as chromosome microarray analysis using CytoScan HD chip.Results The proband and her father and grandfather were found to carry a deletion for position 85 992 693-86 842 693 on chromosome 2,which spanned about 900 kb and encompassed the REEP1 gene.The latter has been specifically associated with hereditary spastic paraplegia type 31.The same deletion was not found in her mother who is phenotypically normal.Conclusion The deletional variation of the REEP1 gene probably underlies the disease in this pedigree.