Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia.
J Med Genet
; 53(7): 457-64, 2016 07.
Article
em En
| MEDLINE
| ID: mdl-27068007
ABSTRACT
BACKGROUND:
Acromelic dysplasias are a group of disorders characterised by short stature, brachydactyly, limited joint extension and thickened skin and comprises acromicric dysplasia (AD), geleophysic dysplasia (GD), Myhre syndrome and Weill-Marchesani syndrome. Mutations in several genes have been identified for these disorders (including latent transforming growth factor ß (TGF-ß)-binding protein-2 (LTBP2), ADAMTS10, ADAMSTS17 and fibrillin-1 (FBN1) for Weill-Marchesani syndrome, ADAMTSL2 for recessive GD and FBN1 for AD and dominant GD), encoding proteins involved in the microfibrillar network. However, not all cases have mutations in these genes.METHODS:
Individuals negative for mutations in known acromelic dysplasia genes underwent whole exome sequencing.RESULTS:
A heterozygous missense mutation (exon 14 c.2087C>G p.Ser696Cys) in latent transforming growth factor ß (TGF-ß)-binding protein-3 (LTBP3) was identified in a dominant AD family. Two distinct de novo heterozygous LTPB3 mutations were also identified in two unrelated GD individuals who had died in early childhood from respiratory failure-a donor splice site mutation (exon 12 c.1846+5G>A) and a stop-loss mutation (exon 28 c.3912A>T p.1304*Cysext*12).CONCLUSIONS:
The constellation of features in these AD and GD cases, including postnatal growth retardation of long bones and lung involvement, is reminiscent of the null ltbp3 mice phenotype. We conclude that LTBP3 is a novel component of the microfibrillar network involved in the acromelic dysplasia spectrum.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças do Desenvolvimento Ósseo
/
Deformidades Congênitas dos Membros
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Mutação de Sentido Incorreto
/
Proteínas de Ligação a TGF-beta Latente
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article