Disease relevance of SMARCAL1

• For SMARCAL1 mutations a clear genotype-phenotype correlation has been reported: severe SIOD with in utero or early-childhood onset leading to end-stage renal disease within a few years is caused by nonsense, frame shift or splice mutations [1].
• Autosomal-recessive Schimke immuno-osseous dysplasia (SIOD) characterized by spondyloepiphyseal dysplasia, focal-segmental glomerulosclerosis (FSGS), T-cell immunodeficiency and facial dysmorphism is caused by defects in the SMARCAL1 gene [1].
• We report a patient with SIOD and SMARCAL1 mutations, who presented with fever of unknown origin secondary to B-cell lymphoma [2].

High impact information on SMARCAL1

• Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia [3].
• These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease [3].
• HARP/SMARCAL1 transcripts are ubiquitously expressed in human and mouse tissues, with testis presenting the highest levels of mRNA expression in humans [4].
• 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 [5].
• 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 [5].

Biological context of SMARCAL1

• 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 [5].

Anatomical context of SMARCAL1

• The Smarcal1 mRNA and protein were expressed throughout development and in all tissues affected in patients with SIOD including the bone, kidney, thymus, thyroid, tooth, bone marrow, hair, eye, and blood vessels [6].

Associations of SMARCAL1 with chemical compounds

• Biallelic mutations in switch/sucrose nonfermenting (swi/snf) related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD [5].

Analytical, diagnostic and therapeutic context of SMARCAL1

• 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 [3].

References