Mutations in the gene kyphoscoliosis peptidase (KY) are known to cause myofibrillar myopathy-7 and hereditary spastic paraplegia. We investigated the genetic cause of a complex neurological phenotype in a consanguineous Pakistani family with four affected members, manifesting lower limb spasticity and weakness, toe walking, pes equinovarus, and a speech disorder. Genome-wide linkage analysis with microsatellite markers delineated chromosome 3q22.2-q24 harboring the disease gene. Whole exome sequencing was performed for two subjects, identifying a homozygous 14-bp frameshift deletion NM_178554.6:c.842_855del; p(Val281GlyfsTer18) in KY. The variant segregated with the phenotype and was absent from public databases and 100 ethnically matched controls. We confirm a novel homozygous KY variant causing a complex neurological phenotype in this family. A review of previously reported KY variants suggests that variants in this gene can cause a spectrum of neurological phenotypes.

众所周知，脊柱后凸肽酶( KY )基因突变会导致肌原纤维肌病-7 和遗传性痉挛性截瘫。我们在一个有四名受影响成员的近亲巴基斯坦家庭中调查了复杂神经表型的遗传原因，表现出下肢痉挛和虚弱、脚趾走路、马蹄内翻和言语障碍。使用微卫星标记的全基因组连锁分析描绘了含有疾病基因的染色体 3q22.2-q24。对两名受试者进行了全外显子组测序，鉴定了纯合 14-bp 移码缺失 NM_178554.6:c.842_855del；p(Val281GlyfsTer18) 在KY. 该变体与表型分离，在公共数据库和 100 个种族匹配的对照中不存在。我们确认了一种新的纯合KY变体，该变体在该家族中引起了复杂的神经表型。对先前报道的KY变异的回顾表明，该基因的变异可导致一系列神经表型。