Phenotypic and molecular characterization of Cornelia de Lange syndrome caused by heterozygous missense variant in the NIPBL gene
Objective To investigate the clinical characteristics and genetic basis of Cornelia de Lange syndrome(CdLS)in a child.Methods The study focused on a proband admitted to the Department of Pediatrics at the First Affiliated Hospital of Wenzhou Medical University in July 2023,presenting with intellectual disability and developmental delay.Ge-nomic DNA was extracted from the proband's peripheral blood sample,and whole-exome sequencing(WES)was performed to identify potential pathogenic variants.The identified variant was further confirmed by Sanger sequencing.Bioinformatic analysis was employed to predict and validate the variant's impact.Results A de novo missense variant,c.7168G＞A(p.A2390T),was identified in the NIPBL gene of the proband.This variant had not been previously reported and was predicted to be pathogenic by multiple prediction tools,including Poly-2,MutationTaster CADD and REVEL.The variant was absent in ma-jor population databases,including ExAC,1000G and dbSNP.Based on the American College of Medical Genetics and Ge-nomics(ACMG)guidelines,the variant was classified as pathogenic.Conclusion The c.7168G＞A(p.A2390T)missense vari-ant is likely responsible for the CdLS in this patient.Genetic testing has been instrumental in diagnosing this condition.
NIPBL geneCornelia de Lange syndromede novo variantmissense variant
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NSTL
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