Comprehensive review and expanding the genetic landscape of Cornelia-de-Lange spectrum: insights from novel mutations and skin biopsy in exome-negative cases-Reference-Cited by-同舟云学术

Comprehensive review and expanding the genetic landscape of Cornelia-de-Lange spectrum: insights from novel mutations and skin biopsy in exome-negative cases

Published:2024-01-12 Issue:1 Volume:17 Page:
ISSN:1755-8794
Container-title:BMC Medical Genomics
language:en
Short-container-title:BMC Med Genomics

Author:

Tehrani Fateh Sahand^ORCID,Mohammad Zadeh Nadia^ORCID,Salehpour Shadab^ORCID,Hashemi-Gorji Farzad^ORCID,Omidi Ashkan^ORCID,Sadeghi Hossein^ORCID,Mirfakhraie Reza^ORCID,Moghimi Parinaz^ORCID,Keyvanfar Sepideh^ORCID,Mohammadi Sarvaleh Sepideh,Miryounesi Mohammad^ORCID,Ghasemi Mohammad-Reza^ORCID

Abstract

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.

Publisher

Springer Science and Business Media LLC

Link

https://link.springer.com/content/pdf/10.1186/s12920-024-01798-7.pdf

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