title: Exome Sequencing of a Pedigree Reveals S339L Mutation in the TLN2 Gene as a Cause of Fifth Finger Camptodactyly.
abstract: Camptodactyly is a digit deformity characterized by permanent flexion contracture of one or both fifth fingers at the proximal interphalangeal joints. Though over 60 distinct types of syndromic camptodactyly have been described, only one disease locus (3q11.2-q13.12) for nonsyndromic camptodactyly has been identified. To identify the genetic defect for camptodactyly in a four-generation Chinese Han family, exome and Sanger sequencings were conducted and a missense variant, c.1016C>T (p.S339L), in the talin 2 gene (TLN2) was identified. The variant co-segregated with disease in the family and was not observed in 12 unaffected family members or 1,000 normal controls, suggesting that p.S339L is a pathogenic mutation. Two asymptomatic carriers in the family indicated incomplete penetrance or more complicated compensated mechanism. Most of p.S339L carriers also have relatively benign cardiac phenotypes. Expression of wild and mutant TLN2 in HEK293 cells suggested the predominant localization in cytoplasm. Our data suggest a potential molecular link between TLN2 and camptodactyly pathogenesis.
authors.affiliation: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.affiliation: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.|Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Deng
authors.affiliation: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xu
authors.affiliation: Division of Neuromuscular Medicine, Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, United States of America.
authors.forename: Han-Xiang
authors.initials: HX
authors.lastname: Deng
authors.affiliation: Beijing Genomics Institute-Shenzhen, Shenzhen, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Lamei
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Dermatology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Shengbo
authors.initials: S
authors.lastname: Yang
authors.affiliation: Beijing Genomics Institute-Shenzhen, Shenzhen, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: Beijing Genomics Institute-Shenzhen, Shenzhen, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Center for Experimental Medicine and Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.|Information Security and Big Data Research Institute, Central South University, Changsha, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D044466:Asian People; D002681:China; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D059472:Exome; D005260:Female; D005385:Fingers / Q000002:abnormalities; D057809:HEK293 Cells; D006228:Hand Deformities, Congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D021381:Protein Transport / Q000235:genetics; D016608:Talin / Q000235:genetics / Q000378:metabolism
chemical_list: C436513:TLN2 protein, human; D016608:Talin