Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome.
Hum Mutat
; 29(8): 1017-27, 2008 Aug.
Article
em En
| MEDLINE
| ID: mdl-18425797
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Morfogenéticas Ósseas
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Síndrome de Klippel-Feil
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article