TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome.

Détails

ID Serval
serval:BIB_7490303FB7A8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome.
Périodique
American Journal of Human Genetics
Auteur(s)
Lausch E., Hermanns P., Farin H.F., Alanay Y., Unger S., Nikkel S., Steinwender C., Scherer G., Spranger J., Zabel B., Kispert A., Superti-Furga A.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Statut éditorial
Publié
Date de publication
2008
Volume
83
Numéro
5
Pages
649-655
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Résumé
Members of the evolutionarily conserved T-box family of transcription factors are important players in developmental processes that include mesoderm formation and patterning and organogenesis both in vertebrates and invertebrates. The importance of T-box genes for human development is illustrated by the association between mutations in several of the 17 human family members and congenital errors of morphogenesis that include cardiac, craniofacial, and limb malformations. We identified two unrelated individuals with a complex cranial, cervical, auricular, and skeletal malformation syndrome with scapular and pelvic hypoplasia (Cousin syndrome) that recapitulates the dysmorphic phenotype seen in the Tbx15-deficient mice, droopy ear. Both affected individuals were homozygous for genomic TBX15 mutations that resulted in truncation of the protein and addition of a stretch of missense amino acids. Although the mutant proteins had an intact T-box and were able to bind to their target DNA sequence in vitro, the missense amino acid sequence directed them to early degradation, and cellular levels were markedly reduced. We conclude that Cousin syndrome is caused by TBX15 insufficiency and is thus the human counterpart of the droopy ear mouse.
Mots-clé
Body Height/genetics, Child, Craniofacial Abnormalities/genetics, Craniofacial Abnormalities/radiography, Female, Humans, Mutation, Mutation, Missense, Pelvis/pathology, Pelvis/radiography, Scapula/pathology, Scapula/radiography, Syndrome, T-Box Domain Proteins/genetics, T-Box Domain Proteins/metabolism, Young Adult
Pubmed
Web of science
Création de la notice
14/03/2011 17:09
Dernière modification de la notice
03/03/2018 18:21
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