title: Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.
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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. boerkoel@bcm.tmc.edu
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.forename: Joy
authors.initials: J
authors.lastname: John
authors.forename: Jiong
authors.initials: J
authors.lastname: Yan
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Lisa
authors.initials: L
authors.lastname: Rosenbarker
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: André
authors.forename: Radovan
authors.initials: R
authors.lastname: Bogdanovic
authors.forename: Antoine
authors.initials: A
authors.lastname: Burguet
authors.forename: Sandra
authors.initials: S
authors.lastname: Cockfield
authors.forename: Isabel
authors.initials: I
authors.lastname: Cordeiro
authors.forename: Stefan
authors.initials: S
authors.lastname: Fründ
authors.forename: Friederike
authors.initials: F
authors.lastname: Illies
authors.forename: Mark
authors.initials: M
authors.lastname: Joseph
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kaitila
authors.forename: Giuliana
authors.initials: G
authors.lastname: Lama
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
authors.forename: D Ross
authors.initials: DR
authors.lastname: McLeod
authors.forename: David V
authors.initials: DV
authors.lastname: Milford
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Petty
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodrigo
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Saraiva
authors.forename: Beate
authors.initials: B
authors.lastname: Schmidt
authors.forename: Graham C
authors.initials: GC
authors.lastname: Smith
authors.forename: Jürgen
authors.initials: J
authors.lastname: Spranger
authors.forename: Anja
authors.initials: A
authors.lastname: Stein
authors.forename: Hannelore
authors.initials: H
authors.lastname: Thiele
authors.forename: Jane
authors.initials: J
authors.lastname: Tizard
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: David W
authors.initials: DW
authors.lastname: Stockton
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D051437:Renal Insufficiency / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D004247:DNA; C412482:SMARCAL1 protein, human; D004265:DNA Helicases