Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.
Nat Genet
; 30(2): 215-20, 2002 Feb.
Article
em En
| MEDLINE
| ID: mdl-11799392
ABSTRACT
Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.
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Base de dados:
MEDLINE
Assunto principal:
Osteocondrodisplasias
/
DNA Helicases
/
Síndromes de Imunodeficiência
/
Mutação
Tipo de estudo:
Etiology_studies
Limite:
Adolescent
/
Adult
/
Animals
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article