Heterozygous Mutations in MAP3K7, Encoding TGF-ß-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome.
Am J Hum Genet
; 99(2): 407-13, 2016 08 04.
Article
em En
| MEDLINE
| ID: mdl-27426734
ABSTRACT
Cardiospondylocarpofacial (CSCF) syndrome is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. Whole-exome sequencing identified heterozygous MAP3K7 mutations in six distinct CSCF-affected individuals from four families and ranging in age from 5 to 37 years. MAP3K7 encodes transforming growth factor ß (TGF-ß)-activated kinase 1 (TAK1), which is involved in the mitogen-activated protein kinase (MAPK)-p38 signaling pathway. MAPK-p38 signaling was markedly altered when expression of non-canonical TGF-ß-driven target genes was impaired. These findings support the loss of transcriptional control of the TGF-ß-MAPK-p38 pathway in fibroblasts obtained from affected individuals. Surprisingly, although TAK1 is located at the crossroad of inflammation, immunity, and cancer, this study reports MAP3K7 mutations in a developmental disorder affecting mainly cartilage, bone, and heart.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ossos do Tarso
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Ossos do Carpo
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Vértebras Cervicais
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MAP Quinase Quinase Quinases
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Perda Auditiva Condutiva
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Heterozigoto
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Insuficiência da Valva Mitral
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article