Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing.
10.3343/alm.2015.35.6.639
- Author:
Mi Ae JANG
1
;
Chang Woo LEE
;
Jin Kyung KIM
;
Chang Seok KI
Author Information
1. Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea.
- Publication Type:Brief Communication ; Case Reports
- Keywords:
Cornelia de Lange Syndrome;
Exome sequencing;
Mutation;
SMC1A
- MeSH:
Asian Continental Ancestry Group/genetics;
Base Sequence;
Cell Cycle Proteins/*genetics;
Child, Preschool;
Chromosomal Proteins, Non-Histone/*genetics;
DNA;
DNA Mutational Analysis;
De Lange Syndrome/diagnosis/*genetics;
Female;
Heterozygote;
Humans;
Male;
Pedigree;
Phenotype;
Polymorphism, Single Nucleotide;
Proteins/genetics;
Republic of Korea
- From:Annals of Laboratory Medicine
2015;35(6):639-642
- CountryRepublic of Korea
- Language:English
-
Abstract:
Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous congenital anomaly. Mutations in the NIPBL gene account for a half of the affected individuals. We describe a family with CdLS carrying a novel pathogenic variant of the SMC1A gene identified by exome sequencing. The proband was a 3-yr-old boy presenting with a developmental delay. He had distinctive facial features without major structural anomalies and tested negative for the NIPBL gene. His younger sister, mother, and maternal grandmother presented with mild mental retardation. By exome sequencing of the proband, a novel SMC1A variant, c.3178G>A, was identified, which was expected to cause an amino acid substitution (p.Glu1060Lys) in the highly conserved coiled-coil domain of the SMC1A protein. Sanger sequencing confirmed that the three female relatives with mental retardation also carry this variant. Our results reveal that SMC1A gene defects are associated with milder phenotypes of CdLS. Furthermore, we showed that exome sequencing could be a useful tool to identify pathogenic variants in patients with CdLS.
