A Novel Mutation in NIPBL Gene with the Cornelia de Lange Syndrome and a 10q11.22-q11.23 Microdeletion in the Same Individual

Abstract

The Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. CdLS is due to mutations in one of the following genes: NIPBL , SMC1A , SMC3 , RAD21 , and HDAC8 . On the other hand, 10q11.2 deletions cause a wide range of presentations in patients. Approximately 40 cases with variable deletions of 10q11.2 have been reported in literature. Some of the reported cases involve the coexistence of duplication or deletion affecting one copy of the chromosome. However, deletion of chromosome 10q11.22-q11.23 and CdLS syndrome caused by NIPBL gene mutations have not been reported previously. This report, therefore, is the first to report their coexistence together.

Keywords: 10q11.2 micro deletion; NIPBL gene; the Cornelia de Lange syndrome.

Fig.1

Clinical photographs of the patient at 12 years of age. Dysmorphic facial features, including a high arched and thick eyebrows, synophrys, flattened nasal root, antevert nares, pointed jaw, long philtrum, low-set ear, clinodactyly on fifth finger in both hands, and four to five metatarsal bone shortness.

Fig. 2

( A ) Result of CytoScan 315K array exhibiting deletion in 10q11.22 to 10q11.23. ( B ) Targeted next-generation sequencing (MiSeq)] revealed that proband had a novel heterozygous c.245A > G (p.Asn82Ser) variant in NIPBL gene.