SET binding factor 1 (SBF1) mutation causes Charcot-Marie-Tooth disease type 4B3
SET binding factor 1 (SBF1) mutation causes Charcot-Marie-Tooth disease type 4B3
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DOI：
10.1212/wnl.0b013e31829a3421
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发表时间：
2013-07-09
期刊：
影响因子：
9.9
通讯作者：
Chung, Ki Wha
中科院分区：
文献类型：
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作者：
Nakhro, Khriezhanuo;Park, Jin-Mo;Chung, Ki Wha
目的：探讨一常染色体隐性遗传性脱髓鞘Charcot-Marie-Tooth病4B(CMT4B)家系的遗传原因。我们对6个样本(3个患病个体和3个未患病个体)进行了外显子组测序。结果：集合结合因子1(SBF1)基因(22q13.33)的一对杂合错义突变(22q13.33)，也被称为MTMR5，是CMT4B家族疾病的潜在原因。CMT4B患者的临床表型在某种程度上与CMT4B1和CMT4B2患者相似。我们在我们的患者中发现了类似的大的有髓纤维和局灶性折叠的髓鞘丢失，但有髓纤维的实际数量与CMT4B1和CMT4B2不同。结论：SBF1的复合杂合性突变是CMT4B亚型CMT4B3的潜在原因。我们相信，这项研究将导致发现SBF1功能的机制研究和CMT病的分子诊断学的发展。
Objective: To identify the genetic cause of an autosomal recessive demyelinating Charcot-Marie-Tooth disease type 4B (CMT4B) family.Methods: We enrolled 14 members of a Korean family in which 3 individuals had demyelinating CMT4B phenotype and obtained distal sural nerve biopsies from all affected participants. We conducted exome sequencing on 6 samples (3 affected and 3 unaffected individuals).Results: One pair of heterozygous missense mutations in the SET binding factor 1 (SBF1) gene (22q13.33), also called MTMR5, was identified as the underlying cause of the CMT4B family illness. Clinical phenotypes of affected study participants with CMT4B were similar, to some extent, to patients with CMT4B1 and CMT4B2. We found a similar loss of large myelinated fibers and focally folded myelin sheaths in our patients, but the actual number of myelinated fibers was different from CMT4B1 and CMT4B2.Conclusions: We suggest that the compound heterozygous mutations in SBF1 are the underlying causes of a novel CMT4B subtype, designated as CMT4B3. We believe that this study will lead to mechanistic studies to discover the function of SBF1 and to the development of molecular diagnostics for CMT disease.