Genetic characterization of a patient with Cornelia de Lange syndrome with a novel NIPBL missense mutation

Background Cornelia de Lange syndrome (CdLS) is a rare clinically and genetically heterogeneous disease. Cardinal phenotypic manifestations include specific dysmorphic facial features, growth retardation, intellectual disability, and upper limb anomalies. Mutations in five genes including NIPBL, SMC1A, SMC3, RAD21, and HDAC8 are known to be responsible for the syndrome, with the NIPBL gene mutation being the most prevalent (~80%). This study aimed to report the clinical, cytogenetic, and molecular characterization of a patient with CdLS with a heterozygous novel exonic missense mutation of the NIPBL gene. Patients and methods We have studied a male patient of 9 years and 4 months of age who presented with features suggestive of CdLS. Thorough clinical examination, conventional cytogenetic analysis, and molecular study using direct Sanger sequencing were performed. Results Clinical examination favored the diagnosis of CdLS. Conventional cytogenetic analysis revealed a normal 46, XY karyotype, with no evidence of premature sister chromatid separation. Molecular study showed a heterozygous novel exonic missense variant c. 2469G>T; p. (R657I) of the NIPBL gene. Conclusion A novel heterozygous exonic missense variant c. 2469G>T; p. (R657I) of the NIPBL gene was confirmed in our patient with CdLS. The phenotypic severity is probably correlated with the plausible effect of NIPBL gene mutation on the protein product rather than the variant type. The adverse effect of NIPBL gene mutation on the cohesion process mediated by cohesin complex is controversial.