title: IGHMBP2-related clinical and genetic features in a cohort of Chinese Charcot-Marie-Tooth disease type 2 patients.
abstract: IGHMBP2 mutations had been exclusively associated with spinal muscular atrophy with respiratory distress type I. However, increasing AR-CMT2S cases without respiratory failure caused by IGHMBP2 mutations have been reported in the past two years. We detected IGHMBP2 mutations in a cohort of Chinese CMT2 patients using genes panel testing, polymerase chain reaction and Sanger sequencing. We found four families with autosomal recessive IGHMBP2 mutations, and the frequency of IGHMBP2 mutations is 6.5% in CMT2 without dominant inheritance. We detected a homozygous variant c.1235 + 3A > G in Family 1, compound heterozygous variants c.1737C > A and c.2597_2598delAG in Family 2, compound heterozygous variants c.1489G > A and c.2356delG in Family 3, compound heterozygous variants c.1909C > T and c.1061-2A > G in Family 4. According to the standards and guidelines of the American College of Medical Genetics and Genomics, all the above variants were classified as pathogenic. Four mutations, c.1489G > A, c.2356delG, c.2597_2598delAG and c.1061-2A > G, are reported for the first time. The novel splice acceptor site mutation c.1061-2A > G resulted in deletion of 175 bp, and it was predicted to lead to a frameshift after codon 354 with a premature termination at codon 364. In conclusion, mutation screening of IGHMBP2 should be especially considered in AR-CMT2 and sporadic CMT2 patients.
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zi
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, China; Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China. Electronic address: zhangruxu@vip.163.com.
authors.forename: Ruxu
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D002681:China; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors
keywords: Autosomal recessive Charcot–Marie–Tooth type 2S (AR-CMT2S); Gene panel testing; IGHMBP2; Spinal muscular atrophy with respiratory distress type I (SMARD1)