A novel splice site mutation in SMARCAL1 results in aberrant exon definition in a child with schimke immunoosseous dysplasia. (5th May 2015)

• Record Type: Journal Article
• Authors: Carroll, Clinton; Hunley, Tracy E.; Guo, Yan; Cortez, David
• Is Part Of: American journal of medical genetics. Volume 167:Number 10(2015:Oct.)
• Page Start: 2260
• Page End: 2264
• Publication Date: 2015-05-05
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37146
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga37146-sec-0001" sec-type="section"> <p>Schimke Immunoosseous Dysplasia (SIOD) is a rare, autosomal recessive disorder of childhood characterized by spondyloepiphyseal dysplasia, focal segmental glomerulosclerosis and renal failure, T‐cell immunodeficiency, and cancer in certain instances. Approximately half of patients with SIOD are reported to have biallelic mutations in <italic>SMARCAL1</italic> (SWI/SNF‐related matrix‐associated actin‐dependent regulator of chromatin, subfamily a‐like 1), which encodes a DNA translocase that localizes to sites of DNA replication and repairs damaged replication forks. We present a novel mutation (NM_014140.3:c.2070+2insT) that results in defective <italic>SMARCAL1</italic> mRNA splicing in a child with SIOD. This mutation, within the donor site of intron 12, results in the skipping of exon 12, which encodes part of a critical hinge region connecting the two lobes of the ATPase domain. This mutation was not recognized as deleterious by diagnostic <italic>SMARCAL1</italic> sequencing, but discovered through next generation sequencing and found to result in absent <italic>SMARCAL1</italic> expression in patient‐derived lymphoblasts. The splicing defect caused by this mutation supports the concept of exon definition. Furthermore, it illustrates the need to broaden the search for <italic>SMARCAL1</italic> mutations in patients with SIOD lacking coding sequence variants. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>