TY - JOUR
T1 - Schimke immunoosseous dysplasia
T2 - Defining skeletal features
AU - Hunter, Kshamta B.
AU - Lücke, Thomas
AU - Spranger, Jürgen
AU - Smithson, Sarah F.
AU - Alpay, Harika
AU - André, Jean Luc
AU - Asakura, Yumi
AU - Bogdanovic, Radovan
AU - Bonneau, Dominique
AU - Cairns, Robyn
AU - Cransberg, Karlien
AU - Fründ, Stefan
AU - Fryssira, Helen
AU - Goodman, David
AU - Helmke, Knut
AU - Hinkelmann, Barbara
AU - Lama, Guiliana
AU - Lamfers, Petra
AU - Loirat, Chantal
AU - Majore, Silvia
AU - Mayfield, Christy
AU - Pontz, Bertram F.
AU - Rusu, Cristina
AU - Saraiva, Jorge M.
AU - Schmidt, Beate
AU - Shoemaker, Lawrence
AU - Sigaudy, Sabine
AU - Stajic, Natasa
AU - Taha, Doris
AU - Boerkoel, Cornelius F.
N1 - Funding Information:
Acknowledgements The authors thank Drs. Alireza Baradaran-Heravi, Jan M. Friedman, and Judith Hall for critical review of this manuscript. This work was supported in part by grants from the Child & Family Research Institute (C. F. Boerkoel) and the Michael Smith Foundation for Health Research (C. F. Boerkoel).
PY - 2010/7
Y1 - 2010/7
N2 - Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations. Therefore, we analyzed the skeletal radiographs of 22 patients with and 11 without detectable SMARCAL1 mutations. We found that patients with SMARCAL1 mutations have a spondyloepiphyseal dysplasia (SED) essentially limited to the spine, pelvis, capital femoral epiphyses, and possibly the sella turcica, whereas the hands and other long bones are basically normal. Additionally, we found that several of the adolescent and young adult patients developed osteoporosis and coxarthrosis. Of the 11 patients without detectable SMARCAL1 mutations, seven had a SED indistinguishable from patients with SMARCAL1 mutations. We conclude therefore that SED is a feature of patients with SMARCAL1 mutations and that skeletal features do not distinguish who of those with SED have SMARCAL1 mutations.
AB - Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations. Therefore, we analyzed the skeletal radiographs of 22 patients with and 11 without detectable SMARCAL1 mutations. We found that patients with SMARCAL1 mutations have a spondyloepiphyseal dysplasia (SED) essentially limited to the spine, pelvis, capital femoral epiphyses, and possibly the sella turcica, whereas the hands and other long bones are basically normal. Additionally, we found that several of the adolescent and young adult patients developed osteoporosis and coxarthrosis. Of the 11 patients without detectable SMARCAL1 mutations, seven had a SED indistinguishable from patients with SMARCAL1 mutations. We conclude therefore that SED is a feature of patients with SMARCAL1 mutations and that skeletal features do not distinguish who of those with SED have SMARCAL1 mutations.
KW - Genocopy
KW - Immunodeficiency
KW - Locus heterogeneity
KW - Proteinuria
KW - Schimke immunoosseous dysplasia
KW - Skeletal dysplasia
UR - http://www.scopus.com/inward/record.url?scp=77954404245&partnerID=8YFLogxK
U2 - 10.1007/s00431-009-1115-9
DO - 10.1007/s00431-009-1115-9
M3 - Article
AN - SCOPUS:77954404245
VL - 169
SP - 801
EP - 811
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
SN - 0340-6199
IS - 7
ER -