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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 pro...

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Autores principales: Jang, Mi-Ae, Lee, Chang-Woo, Kim, Jin-Kyung, Ki, Chang-Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Laboratory Medicine 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579110/
https://www.ncbi.nlm.nih.gov/pubmed/26354354
http://dx.doi.org/10.3343/alm.2015.35.6.639
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author Jang, Mi-Ae
Lee, Chang-Woo
Kim, Jin-Kyung
Ki, Chang-Seok
author_facet Jang, Mi-Ae
Lee, Chang-Woo
Kim, Jin-Kyung
Ki, Chang-Seok
author_sort Jang, Mi-Ae
collection PubMed
description 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.
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spelling pubmed-45791102015-11-01 Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing Jang, Mi-Ae Lee, Chang-Woo Kim, Jin-Kyung Ki, Chang-Seok Ann Lab Med Brief Communication 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. The Korean Society for Laboratory Medicine 2015-11 2015-09-01 /pmc/articles/PMC4579110/ /pubmed/26354354 http://dx.doi.org/10.3343/alm.2015.35.6.639 Text en © The Korean Society for Laboratory Medicine. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Brief Communication
Jang, Mi-Ae
Lee, Chang-Woo
Kim, Jin-Kyung
Ki, Chang-Seok
Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing
title Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing
title_full Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing
title_fullStr Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing
title_full_unstemmed Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing
title_short Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing
title_sort novel pathogenic variant (c.3178g>a) in the smc1a gene in a family with cornelia de lange syndrome identified by exome sequencing
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579110/
https://www.ncbi.nlm.nih.gov/pubmed/26354354
http://dx.doi.org/10.3343/alm.2015.35.6.639
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