OBJECTIVE To identify the genetic cause of complex neuropathy in two siblings from a consanguineous family. METHODS 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. RESULTS 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. CONCLUSION 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.

中文翻译：

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具有项链纤维的常染色体隐性 SBF1 相关综合征神经病中的一种新的移码缺失。

目的 确定来自近亲家庭的两个兄弟姐妹复杂神经病变的遗传原因。方法 患者从我们的诊所招募。进行了肌肉活检和全外显子组测序（WES）。来自索引患者、未受影响的父母和三个正常对照的成纤维细胞系用于 cDNA 分析和蛋白质印迹。结果 指示患者是一名 29 岁男性，临床表型为并指、高弓足、吞咽困难、视力问题、失衡和肌肉无力。兄弟姐妹有类似的症状，但症状较轻。两名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变。肌肉活检显示项链纤维的特征。WES 鉴定出一种新的纯合移码缺失 (c.5477-5478del; p. 1826-1826del）在两个兄弟姐妹的 SBF1 基因的外显子 40 中，而父母和未受影响的兄弟姐妹都是杂合子携带者。功能分析显示在指示病例中由 SBF1 编码的 MTMR5 蛋白水平显着降低。未受影响的父母中的 MTMR5 蛋白水平与对照组中的相似。结论 在该家族中鉴定了 SBF1 中新的纯合移码缺失。活检中的感觉运动轴索神经病变和项链纤维是扩展 SBF1 相关隐性综合征神经病变表型谱的主要特征。未受影响的父母中的 MTMR5 蛋白水平与对照组中的相似。结论 在该家族中鉴定了 SBF1 中新的纯合移码缺失。活检中的感觉运动轴索神经病变和项链纤维是扩展 SBF1 相关隐性综合征神经病变表型谱的主要特征。未受影响的父母中的 MTMR5 蛋白水平与对照组中的相似。结论 在该家族中鉴定了 SBF1 中新的纯合移码缺失。活检中的感觉运动轴索神经病变和项链纤维是扩展 SBF1 相关隐性综合征神经病变表型谱的主要特征。