Premium
Mutations in GDF6 are associated with vertebral segmentation defects in Klippel‐Feil syndrome
Author(s) -
Tassabehji May,
Fang Zhi Ming,
Hilton Emma N.,
McGaughran Julie,
Zhao Zhongming,
de Bock Charles E.,
Howard Emma,
Malass Michael,
Donnai Dian,
Diwan Ashish,
Manson Forbes D.C.,
Murrell Dédée,
Clarke Raymond A.
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20741
Subject(s) - klippel–feil syndrome , biology , anatomy , segmentation , genetics , artificial intelligence , computer science
Klippel‐Feil syndrome (KFS) is a congenital disorder of spinal segmentation distinguished by the bony fusion of anterior/cervical vertebrae. Scoliosis, mirror movements, otolaryngological, kidney, ocular, cranial, limb, and/or digit anomalies are often associated. Here we report mutations at the GDF6 gene locus in familial and sporadic cases of KFS including the recurrent missense mutation of an extremely conserved residue c.866T>C (p.Leu289Pro) in association with mirror movements and an inversion breakpoint downstream of the gene in association with carpal, tarsal, and vertebral fusions. GDF6 is expressed at the boundaries of the developing carpals, tarsals, and vertebrae and within the adult vertebral disc. GDF6 knockout mice are best distinguished by fusion of carpals and tarsals and GDF6 knockdown in Xenopus results in a high incidence of anterior axial defects consistent with a role for GDF6 in the etiology, diversity, and variability of KFS. Hum Mutat 0,1–11, 2008. © 2008 Wiley‐Liss, Inc.