Novel pathogenic variant (c.3178G>A) in the SMC1A gene in a family with Cornelia de Lange syndrome identified by exome sequencing.
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.
['Jang|Mi Ae|MA|', 'Lee|Chang Woo|CW|', 'Kim|Jin Kyung|JK|', 'Ki|Chang Seok|CS|']
D044466:Asians D001483:Base Sequence D018797:Cell Cycle Proteins D002675:Child, Preschool D002868:Chromosomal Proteins, Non-Histone D004247:DNA D004252:DNA Mutational Analysis D003635:De Lange Syndrome D005260:Female D006579:Heterozygote D006801:Humans D008297:Male D010375:Pedigree D010641:Phenotype D020641:Polymorphism, Single Nucleotide D011506:Proteins D056910:Republic of Korea
SMC1A Cornelia de Lange Syndrome Exome sequencing Mutation