J Genet Med.  2018 Jun;15(1):24-27. 10.5734/JGM.2018.15.1.24.

A family with X-linked Cornelia de Lange syndrome due to a novel SMC1A missense mutation identified by multi-gene panel sequencing

• Hong S
• Lee CG

• KMID: 2435969
• DOI: http://doi.org/10.5734/JGM.2018.15.1.24

Abstract

Cornelia de Lange syndrome (CdLS) is a rare, clinically and genetically heterogeneous, multi-system developmental disorder caused by mutations in genes that encode components of the cohesin complex. X-linked CdLS caused by an SMC1A mutation is an extremely rare disease characterized by phenotypes milder than those of classic CdLS. In the Republic of Korea, based on a literature review, one family with SMC1A-related CdLS with mild phenotypes has been genetically confirmed to date. In this study, we describe the clinical features of a Korean boy with a hemizygous novel missense mutation and his mother with a heterozygous mutation, i.e., c.2447G>A (p.Arg816His) in SMC1A, identified by multi-gene panel sequencing. The proband had a mild phenotype with typical facial features and his mother exhibited a mild, subclinical phenotype. This study expands the clinical spectrum of patients with X-linked CdLS caused by SMC1A variants. Moreover, these findings reinforce the notion that a dominant negative effect in a carrier female with a heterozygous mutation in SMC1A results in a phenotype milder than that in a male patient with the same mutation.

Keyword

SMC1A; De Lange syndrome; X-Linked genes; High-throughput nucleotide sequencing

MeSH Terms

De Lange Syndrome*
Female
Genes, X-Linked
High-Throughput Nucleotide Sequencing
Humans
Male
Mothers
Mutation, Missense*
Phenotype
Rare Diseases
Republic of Korea