Department of Neurology, Dongguk University College of Medicine, Dongguk Unversity Gyeongju Hospital, Gyeongju, Republic of Korea.
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
Sci Rep. 2020 Feb 24;10(1):3295. doi: 10.1038/s41598-020-60374-y.
Hereditary spastic paraplegia (HSP) is a heterogeneous inherited disorder that manifests with lower extremity weakness and spasticity. HSP can be inherited by autosomal dominant, autosomal recessive, and X-linked inheritance patterns. Recent studies have shown that, although rare, mutations in a single gene can lead to multiple patterns of inheritance of HSP. We enrolled the HSP family showing autosomal dominant inheritance and performed genetic study to find the cause of phenotype in this family. We recruited five members of a Korean family as study participants. Four of the five family members had pure HSP. Part of the family members underwent whole-exome sequencing (WES) to identify the causative mutation. As the result of WES and Sanger sequencing analysis, a novel missense mutation (c.452 C > T, p.Ala151Val) of ERLIN2 gene was identified as the cause of the autosomal dominant HSP in the family. Our study suggests that the ERLIN2 gene leads to both autosomal recessive and autosomal dominant patterns of inheritance in HSP. Moreover, autosomal dominant HSP caused by ERLIN2 appears to cause pure HSP in contrast to autosomal recessive ERLIN2 related complicated HSP (SPG18).
遗传性痉挛性截瘫（HSP）是一种表现为下肢无力和痉挛的异质性遗传性疾病。HSP 可通过常染色体显性遗传、常染色体隐性遗传和 X 连锁遗传方式遗传。最近的研究表明，尽管罕见，但单个基因突变可导致 HSP 的多种遗传方式。我们招募了一个表现为常染色体显性遗传的 HSP 家族，并进行了遗传研究，以寻找该家族表型的原因。我们招募了一个韩国家族的五名成员作为研究对象。该家族的五名成员中有四名患有单纯 HSP。部分家族成员接受了全外显子组测序（WES）以确定致病突变。WES 和 Sanger 测序分析的结果表明，该家族的 HSP 为常染色体显性遗传，其原因是 ERLIN2 基因的一个新错义突变（c.452C>T，p.Ala151Val）。我们的研究表明，ERLIN2 基因导致 HSP 同时存在常染色体隐性和常染色体显性遗传方式。此外，与常染色体隐性 ERLIN2 相关的复杂 HSP（SPG18）相比，由 ERLIN2 引起的常染色体显性 HSP 似乎导致单纯 HSP。
