Comprehensive Review and Expanding the Genetic Landscape of Cornelia-De-Lange Spectrum: Insights From Novel Mutations and Skin Biopsy in Exome-Negative Cases Publisher Pubmed



Tehrani Fateh S^{1, 2} ; Mohammad Zadeh N³ ; Salehpour S⁴ ; Hashemigorji F⁵ ; Omidi A³ ; Sadeghi H⁶ ; Mirfakhraie R⁶ ; Moghimi P^{1, 3} ; Keyvanfar S¹ ; Mohammadi Sarvaleh S¹ ; Miryounesi M^{1, 5} ; Ghasemi MR^{1, 6} Show Affiliations
Source: BMC Medical Genomics Published:2024

Abstract

Background: Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder characterized by a range of physical, cognitive, and behavioral abnormalities. This study aimed to perform a comprehensive review of the literature on CdLS and investigate two cases of CdLS with distinct phenotypes that underwent WES to aid in their diagnosis. Methods: We conducted a comprehensive review of the literature on CdLS along with performing whole-exome sequencing on two CdLS patients with distinct phenotypes, followed by Sanger sequencing validation and in-silico analysis. Results: The first case exhibited a classic CdLS phenotype, but the initial WES analysis of blood-derived DNA failed to identify any mutations in CdLS-related genes. However, a subsequent WES analysis of skin-derived DNA revealed a novel heterozygous mutation in the NIPBL gene (NM_133433.4:c.6534_6535del, p.Met2178Ilefs*8). The second case was presented with a non-classic CdLS phenotype, and WES analysis of blood-derived DNA identified a heterozygous missense variant in the SMC1A gene (NM_006306.4:c.2320G>A, p.Asp774Asn). Conclusions: The study shows the importance of considering mosaicism in classic CdLS cases and the value of WES for identifying genetic defects. These findings contribute to our understanding of CdLS genetics and underscore the need for comprehensive genetic testing to enhance the diagnosis and management of CdLS patients. © 2024, The Author(s).