title: Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing.
abstract: Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient's condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases.
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, NT, Hong Kong SAR 999077, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liang
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Tang
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Huishuang
authors.initials: H
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Center for Genetic and Genomic Medicine, Zhejiang University School of Medicine, First Affiliated Hospital and James D. Watson Institute of Genome Sciences, Hangzhou 310006, China.
authors.forename: Tianying
authors.initials: T
authors.lastname: Wei
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China. Electronic address: yix@genomics.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong 518083, China; Center for Genetic and Genomic Medicine, Zhejiang University School of Medicine, First Affiliated Hospital and James D. Watson Institute of Genome Sciences, Hangzhou 310006, China; Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: qiming@genomics.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
mesh_terms: D000293:Adolescent; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods*; D059472:Exome / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005901:Glaucoma / Q000235:genetics; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010375:Pedigree; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C475072:SBF2 protein, human
keywords: Charcot–Marie–Tooth disease; Early-onset glaucoma; SBF2; Whole-exome sequencing