Identification of a novel mutation and polymorphic change in the NIPBL gene of subjects with Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder characterized by distinctive facial dysmorphism, including low anterior hairline, synophrys, anteverted nares, maxillary prognathism, long philtrum, and carp mouth; prenatal and postnatal growth retardation; mental retardation; limb anomalies; and multiple organ defects. The disease is caused by mutations in the NIPBL gene located at 5p13.1. To date, a variety of NIPBL mutations have been identified and shown to be associated with CdLS symptoms. Here, three Taiwanese subjects exhibiting multiple features of CdLS were analyzed in this study. One of the subjects characterized by classic CdLS symptoms had a novel frameshift mutation (C.3196delT) in exonll of the NIPBL gene complex followed by a premature termination codon four amino acids downstream, whereas the two other subjects characterized by less pronounced CdLS symptoms had no detectable mutations in that part of thethe NIPBL gene complex that was analyzed herein. However, the former two subjects had a novel and unreported polymorphism in exon 33 that was also detected in the corresponding allele of 77 of 200 healthy Taiwanese control subjects. In conclusion, we report a novel NIPBL mutation likely associated with CdLS and one new polymorphism that is likely not related to CdLS. These observations suggest that truncating mutations were generally associated with a more severe phenotype. Additional studies using an expanded population of CdLS patients are being performed to enhance our understanding of the role of NIPBL in CdLS pathogenesis.