Department of Neurology, Peking University First Hospital, Beijing, 100034, People's Republic of China.
Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
J Neurol. 2020 Sep;267(9):2705-2712. doi: 10.1007/s00415-020-09827-y. Epub 2020 May 22.
To identify the genetic cause of complex neuropathy in two siblings from a consanguineous family.
The patients were recruited from our clinic. Muscle biopsy and whole-exome sequencing (WES) were performed. Fibroblasts cell lines from the index patient, unaffected parents, and three normal controls were used for cDNA analysis and western blot.
The index patient was a 29-year-old male with clinical phenotype of syndactyly, pes cavus, swallowing difficulties, vision problem, imbalance, and muscle weakness. The sibling had similar, but milder symptoms. Nerve conduction studies and electromyography of both patients suggested sensory-motor axonal neuropathy. Muscle biopsy showed a feature of necklace fibres. WES identified a novel homozygous frameshift deletion (c.5477-5478del; p.1826-1826del) in exon 40 of the SBF1 gene in the two siblings, while both parents and the unaffected sibling were heterozygous carriers. Functional analysis showed a markedly reduced level of MTMR5 protein encoded by SBF1 in the index case. The levels of MTMR5 protein in unaffected parents were similar to those found in controls.
A novel homozygous frameshift deletion in SBF1 was identified in this family. Sensory-motor axonal neuropathy and necklace fibres in biopsy were the major features expanding the phenotypic spectrum of SBF1-related recessive syndromic neuropathy.
鉴定来自近亲家庭的 2 位兄弟姐妹复杂神经病变的遗传病因。
从我们的诊所招募患者。进行肌肉活检和全外显子组测序（WES）。使用索引患者、未受影响的父母和 3 个正常对照的成纤维细胞系进行 cDNA 分析和 Western blot。
索引患者是一名 29 岁男性，具有并指、高弓足、吞咽困难、视力问题、失衡和肌肉无力的临床表型。其同胞具有类似但较轻的症状。两位患者的神经传导研究和肌电图均提示感觉运动轴索性神经病。肌肉活检显示项链纤维特征。WES 在两位患者的 SBF1 基因外显子 40 中发现了一种新的纯合移码缺失（c.5477-5478del；p.1826-1826del），而父母和未受影响的同胞均为杂合携带者。功能分析显示，索引病例中由 SBF1 编码的 MTMR5 蛋白水平显著降低。未受影响的父母的 MTMR5 蛋白水平与对照中发现的水平相似。
在该家族中鉴定出 SBF1 的一种新的纯合移码缺失。活检中的感觉运动轴索性神经病和项链纤维是扩展 SBF1 相关隐性综合征性神经病表型谱的主要特征。
