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Response to Lefebvre et al
Author(s) -
Takeda K.,
Kou I.,
Kawakami N.,
Yasuhiko Y.,
Ogura Y.,
Imagawa E.,
Miyake N.,
Matsumoto N.,
Sudo H.,
Kotani T.,
Nakamura M.,
Matsumoto M.,
Watanabe K.,
Ikegawa S.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13011
Subject(s) - missense mutation , compound heterozygosity , haplotype , genetics , heterozygote advantage , biology , mutation , gene , genotype
Congenital scoliosis (CS) is a common vertebral malformation with incidence of up to 1 of 1000 births worldwide. Recently, TBX6 has been reported as the first disease gene for CS: about 10% of CS patients are compound heterozygotes of rare null mutations and a common haplotype composed by 3 SNPs in TBX6. Lefebvre et al in this journal reported that 2 patients with spondylocostal dysostosis (SCD), a rare skeletal dysplasia affecting spine and ribs also have TBX6 mutations: 1 carried the microdeletion and a rare missense variant, and another 2 rare missense variants. We investigated the pathogenicity of the 3 missense variants in SCD by a luciferase assay. The results were negative for the proposal of Lefebvre et al. We consider these 2 SCD patients are more probably compound heterozygotes of null mutations and a common risk haplotype just as CS patients with TBX6 mutations.