Open AccessA novel compound heterozygous variant in SMARCAL1 leading to mild Schimke immune-osseous dysplasia identified using whole-exome sequencing
Author(s) -
Li Wang,
Jingjing Li,
Wei Ge,
Xiangdong Kong
Publication year - 2021
Publication title -
journal of international medical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.421
H-Index - 57
eISSN - 1473-2300
pISSN - 0300-0605
DOI - 10.1177/03000605211010644
Subject(s) - missense mutation , compound heterozygosity , medicine , exome sequencing , genetics , mutation , phenotype , allele , exon , gene , biology
Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive inherited disorder that is caused by the SMARCAL1 mutation. The phenotype can vary from mild to severe on the basis of the patient’s age at onset. Herein, we report the case of a 14-year-old Chinese boy who presented with short stature, focal segmental glomerulosclerosis (FSGS), and facial dysmorphism. Genetic analysis revealed two compound heterozygous missense mutations, including a well-known mutation (c.1933C>T, p.R645C) and a novel mutation (c.2479G>A, p.V827M) in the SMARCAL1 gene, which were inherited from his parents. In silico analyses showed that the c.2479G>A (p.V827M) variant affects a highly conserved residue within the ATPase catalytic domain. Finally, we established the diagnosis of mild SIOD and treated the patient with diuretics and angiotensin receptor blockers. This report expands the mutational spectrum of SMARCAL1 and reinforces the importance of a detailed clinical evaluation, molecular detection, and appropriate genetic counseling.