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 , and are known to be responsible for the syndrome, with the 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 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 gene.
Conclusion
A novel heterozygous exonic missense variant c. 2469G>T; p. (R657I) of the gene was confirmed in our patient with CdLS. The phenotypic severity is probably correlated with the plausible effect of gene mutation on the protein product rather than the variant type. The adverse effect of gene mutation on the cohesion process mediated by cohesin complex is controversial.