TBX6 null variants and a common hypomorphic allele in congenital scoliosis.

TitleTBX6 null variants and a common hypomorphic allele in congenital scoliosis.
Publication TypeJournal Article
Year of Publication2015
AuthorsWu, N, Ming, X, Xiao, J, Wu, Z, Chen, X, Shinawi, M, Shen, Y, Yu, G, Liu, J, Xie, H, Gucev, ZS, Liu, S, Yang, N, Al-Kateb, H, Chen, J, Zhang, J, Hauser, N, Zhang, T, Tasic, V, Liu, P, Su, X, Pan, X, Liu, C, Wang, L, Shen, J, Shen, J, Chen, Y, Zhang, T, Zhang, J, Choy, KW, Wang, J, Wang, Q, Li, S, Zhou, W, Guo, J, Wang, Y, Zhang, C, Zhao, H, An, Y, Zhao, Y, Wang, J, Liu, Z, Zuo, Y, Tian, Y, Weng, X, Sutton, VR, Wang, H, Ming, Y, Kulkarni, S, Zhong, TP, Giampietro, PF, Dunwoodie, SL, Cheung, SW, Zhang, X, Jin, L, Lupski, JR, Qiu, G, Zhang, F
JournalN Engl J Med
Volume372
Issue4
Pagination341-50
Date Published2015 Jan 22
ISSN1533-4406
KeywordsAdolescent, Asian Continental Ancestry Group, Child, Child, Preschool, Chromosomes, Human, Pair 16, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Mutation, Pedigree, Phenotype, Radiography, Scoliosis, Sequence Deletion, Spine, T-Box Domain Proteins
Abstract

BACKGROUND: Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis.

METHODS: We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multicenter series of 42 persons with 16p11.2 deletions.

RESULTS: We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P

CONCLUSIONS: Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. (Funded by the National Basic Research Program of China and others.).
DOI10.1056/NEJMoa1406829
Alternate JournalN. Engl. J. Med.
PubMed ID25564734
PubMed Central IDPMC4326244
Grant ListR01 NS058529 / NS / NINDS NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
R01NS058529 / NS / NINDS NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States