A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres
A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres
复制标题
常染色体隐性遗传 SBF1 相关综合征性神经病与项链纤维的新型移码缺失
DOI：
10.1007/s00415-020-09827-y
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发表时间：
2020-05
影响因子：
6
通讯作者：
Houlden Henry
中科院分区：
文献类型：
--
作者：
Gang Qiang;Bettencourt Conceicao;Holton Janice;Lovejoy Christopher;Chelban Viorica;O'Connor Emer;Yuan Yun;Reilly Mary M.;Hanna Michael;Houlden Henry
目的
目的探讨一个近亲家系中两兄弟姐妹复杂性神经病的遗传病因。
方法
这些病人是从我们诊所招募的。进行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
索引患者是一名29岁的男性，临床表现为并指、高弓足、吞咽困难、视力问题、失衡和肌无力。兄弟姐妹有类似的症状，但症状较轻。神经传导研究和肌电图的两名患者建议感觉运动轴突神经病。肌肉活检显示项链纤维的特征。WES在两个兄弟姐妹的SBF 1基因外显子40中鉴定出一种新的纯合移码缺失（c.5477- 5478 del; p.1826- 1826 del），而父母和未受影响的兄弟姐妹都是杂合携带者。功能分析显示，在索引情况下，由SBF 1编码的MTMR 5蛋白水平显着降低。未受影响的父母MTMR 5蛋白水平与对照组相似。
结论
一个新的纯合移码缺失SBF 1被确定在这个家庭。感觉运动轴索神经病变和项链纤维活检的主要特点扩大了表型谱SBF 1相关的隐性综合征神经病变。
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.
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影响因子：
3.6
作者：
Kuzmin, Anastasia;Jarvi, Keith;Varmuza, Susannah
通讯作者：
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影响因子：
9.9
作者：
Nakhro, Khriezhanuo;Park, Jin-Mo;Chung, Ki Wha
通讯作者：
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DOI：
10.1172/jci12589
发表时间：
2002-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
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通讯作者：
R. Firestein;P. L. Nagy;M. Daly;P. Huie;M. Conti;M. Cleary
影响因子：
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作者：
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通讯作者：
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影响因子：
2.2
作者：
Manole, Andreea;Horga, Alejandro;Houlden, Henry
通讯作者：
Houlden, Henry