SOX14 is a candidate gene for limb defects associated with BPES and Möbius syndrome.
Members of the SOX gene family encode proteins with homology to the HMG box DNA-binding domain of SRY, the Y-linked testis-determining gene. SOX genes are expressed during embryogenesis and are involved in the development of a wide range of different tissues. Mutations in SRY, SOX9 and SOX10 have been shown to be responsible for XY sex reversal, campomelic dysplasia and Waardenburg-Hirschsprung disease, respectively. It is likely that mutations in other SOX genes are responsible for a variety of human genetic diseases. SOX14 has been identified from a human genomic library and the mouse and chicken sequences obtained by polymerase chain reaction amplification. The SOX14 amino acid sequence is highly conserved across these species, suggesting an important role for this protein in vertebrate development. SOX14 is expressed in the neural tube and apical ectodermal ridge of the developing chicken limb. This is the only SOX gene known to be expressed in the apical ectodermal ridge, a structure that directs outgrowth of the embryonic limb bud. Human SOX14 is localised to a 1.15-Mb yeast artificial chromosome on chromosome 3q23, close to loci for BPES (blepharophimosis, ptosis, epicanthus inversus syndrome) and Mobius syndrome. Although SOX14 maps outside these loci, its expression pattern and chromosomal localisation suggest that it is a candidate gene for the limb defects frequently associated with these syndromes.
Wilmore
H P
HP
Department of Paediatrics and Centre for Hormone Research, The University of Melbourne, Royal Children's Hospital, Australia.
Smith
M J
MJ
Wilcox
S A
SA
Bell
K M
KM
Sinclair
A H
AH
D000595:Amino Acid Sequence; D000818:Animals; D016569:Blepharophimosis / Q000235:genetics*; D001763:Blepharoptosis / Q000235:genetics*; D002642:Chick Embryo; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002893:Chromosomes, Human, Pair 3; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008297:Male; D051379:Mice; D020331:Mobius Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D055749:SOXB2 Transcription Factors; D017386:Sequence Homology, Amino Acid
D006609:High Mobility Group Proteins; C117478:SOX14 protein, human; D055749:SOXB2 Transcription Factors; C492175:Sox14 protein, mouse