| Literature DB >> 11799392 |
Cornelius F Boerkoel1, Hiroshi Takashima, Joy John, Jiong Yan, Pawel Stankiewicz, Lisa Rosenbarker, Jean-Luc André, Radovan Bogdanovic, Antoine Burguet, Sandra Cockfield, Isabel Cordeiro, Stefan Fründ, Friederike Illies, Mark Joseph, Ilkka Kaitila, Giuliana Lama, Chantal Loirat, D Ross McLeod, David V Milford, Elizabeth M Petty, Francisco Rodrigo, Jorge M Saraiva, Beate Schmidt, Graham C Smith, Jürgen Spranger, Anja Stein, Hannelore Thiele, Jane Tizard, Rosanna Weksberg, James R Lupski, David W Stockton.
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.Entities:
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Year: 2002 PMID： 11799392 DOI： 10.1038/ng821
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330