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SBF1基因相关的常染色体隐性遗传神经肌肉病综合征新突变,一个家系报道

作者:刚蔷 等 日期:2019-12-04 浏览量:239

第七届北京罕见病学术大会暨2019京津冀罕见病学术大会征文(132)

1.北京大学第一医院

2.Institute of Neurology, University College of London, UK

刚蔷1,2, Bettencourt C 2, Holton J2, Lovejoy C2, Hersheson J2, Chelban V2, Oconnor E2, Hughes D2,袁云1,Houlden H 2

Aim:To identify the genetic culprit for two siblings with complex neuropathy.

Methods:The siblings were from a consanguineous family that parents are second cousins. The proband was 29yr male, who had syndactyly of two fingers and toes with pes cavus of feet. He started walking by age of one and half, with clumsiness at the age of three. Over few years, he showed slowness of swallowing, choking on food, blurred and double vision, imbalance, dragging his legs, easy fatigue and weakness. He had a tonic pupil with failure of the parasympathetic outflow and sensory loss in a glove and stocking distribution. The sibling had similar symptoms. NCS and EMG of both patients suggested sensory-motor axonal neuropathy. Muscle biopsy and Whole-exome sequencing (WES) was performed in the index patient. Fibroblasts cell lines from index patient, unaffected parents and three normal controls were used for cDNA analysis. Protein from the above fibroblasts cell lines was used for western blot.  Results: Muscle biopsy showed myopathy with prominent internal nuclei and necklace fibres. WES identified a novel homozygous frameshift deletion (c.5477-5478del; p.1826-1826del) in exon 40 of the SBF1 gene in the proband and affected sister, while both parents and the unaffected sibling were heterozygous carriers of the deletion in SBF1. Functional analysis showed a markedly reduced level of MTMR5 protein in the proband. The levels of MTMR5 protein in unaffected parents were similar.  Conclusion:We reported a novel homozygous frameshift deletion in SBF1 in a family with a rare form of neuropathy with necklace fibres. Our findings expand the phenotypic spectrum of SBF1-related recessive neuromyopathy.