Title: Schimke immunoosseous dysplasia: suggestions of genetic diversity
Authors: Clewing, J Marietta ×
Fryssira, Helen
Goodman, David
Smithson, Sarah F
Sloan, Emily A
Lou, Shu
Huang, Yan
Choi, Kunho
Lücke, Thomas
Alpay, Harika
André, Jean-Luc
Asakura, Yumi
Biebuyck-Gouge, Nathalie
Bogdanovic, Radovan
Bonneau, Dominique
Cancrini, Caterina
Cochat, Pierre
Cockfield, Sandra
Collard, Laure
Cordeiro, Isabel
Cormier-Daire, Valerie
Cransberg, Karlien
Cutka, Karel
Deschenes, Georges
Ehrich, Jochen H H
Fründ, Stefan
Georgaki, Helen
Guillen-Navarro, Encarna
Hinkelmann, Barbara
Kanariou, Maria
Kasap, Belde
Kilic, Sara Sebnem
Lama, Guiliana
Lamfers, Petra
Loirat, Chantal
Majore, Silvia
Milford, David
Morin, Denis
Ozdemir, Nihal
Pontz, Bertram F
Proesmans, Willem
Psoni, Stavroula
Reichenbach, Herbert
Reif, Silke
Rusu, Cristina
Saraiva, Jorge M
Sakallioglu, Onur
Schmidt, Beate
Shoemaker, Lawrence
Sigaudy, Sabine
Smith, Graham
Sotsiou, Flora
Stajic, Natasa
Stein, Anja
Stray-Pedersen, Asbjørg
Taha, Doris
Taque, Sophie
Tizard, Jane
Tsimaratos, Michel
Wong, Newton A C S
Boerkoel, Cornelius F #
Issue Date: Nov-2006
Publisher: John Wiley & Sons, Inc.
Series Title: Human Mutation
Abstract: Schimke immunoosseous dysplasia (SIOD), which is characterized by prominent spondyloepiphyseal dysplasia, T-cell deficiency, and focal segmental glomerulosclerosis, is a panethnic autosomal recessive multisystem disorder with variable expressivity. Biallelic mutations in switch/sucrose nonfermenting (swi/snf) &!ndash;related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD. However, among 72 patients from different families, we identified only 38 patients with biallelic mutations in the coding exons and splice junctions of the SMARCAL1 gene. This observation, the variable expressivity, and poor genotype-phenotype correlation led us to test several hypotheses including modifying haplotypes, oligogenic inheritance, or locus heterogeneity in SIOD. Haplotypes associated with the two more common mutations, R820H and E848X, did not correlate with phenotype. Also, contrary to monoallelic SMARCAL1 coding mutations indicating oligogenic inheritance, we found that all these patients did not express RNA and/or protein from the other allele and thus have biallelic SMARCAL1 mutations. We hypothesize therefore that the variable expressivity among patients with biallelic SMARCAL1 mutations arises from environmental, genetic, or epigenetic modifiers. Among patients without detectable SMARCAL1 coding mutations, our analyses of cell lines from four of these patients showed that they expressed normal levels of SMARCAL1 mRNA and protein. This is the first evidence for nonallelic heterogeneity in SIOD. From analysis of the postmortem histopathology from two patients and the clinical data from most patients, we propose the existence of endophenotypes of SIOD. Hum Mutat 0, 1-11, 2006. Published 2006, Wiley-Liss, Inc.
ISSN: 1059-7794
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Section Child - Miscellaneous (-)
× corresponding author
# (joint) last author

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