Identification of a novel de novo mutation in the NIPBL gene in an Iranian patient with Cornelia de Lange syndrome: A case report

Hamid Galehdari,Gholamreza Mohamadian,Roya Monajemzadeh,Habibolah Nazem,Mohammad Pedram

doi:10.1186/1752-1947-5-242

Abstract

BackgroundCornelia de Lange syndrome is characterized by dysmorphic facial features, hirsutism, severe growth and developmental delay. Germline mutations in the NIPBL gene with an autosomal dominant pattern and in the SMC1A gene with an X-linked pattern have been identified in Cornelia de Lange syndrome.Case presentationA two-month-old Iranian boy who showed multiple congenital anomalies was referred to the genetic center of a welfare organization in southwest Iran. He was the second child of a non-consanguineous marriage, born after full term with normal delivery. His birth weight was 3110 g, his length was 46 cm and his head circumference was 30 cm. Both parents were clinically asymptomatic, with no positive history of any deformity in their respective families.ConclusionsSequencing of the NIPBL gene from our patient revealed a single-base deletion of thymidine in exon 10 (c.516delT). This mutation presumably results in premature termination at codon 526. We did not observe this mutation in the parents of our patient with Cornelia de Lange syndrome. The results presented here enlarge the spectrum of NIPBL gene mutations associated with Cornelia de Lange syndrome by identifying a novel de novo mutation in an Iranian patient with Cornelia de Lange syndrome and further support the hypothesis that NIPBL mutations are disease-causing mutations leading to Cornelia de Lange syndrome.

Highlights

We did not observe this mutation in the parents of our patient with Cornelia de Lange syndrome
The results presented here enlarge the spectrum of NIPBL gene mutations associated with Cornelia de Lange syndrome by identifying a novel de novo mutation in an Iranian patient with Cornelia de Lange syndrome and further support the hypothesis that NIPBL mutations are disease-causing mutations leading to Cornelia de Lange syndrome
Cornelia de Lange syndrome (CdLS; http://www.ncbi. nlm.nih.gov/omim/122470), known as Brachmannde Lange syndrome, is a clinically and genetically heterogeneous developmental disorder characterized by growth and mental retardation [1,2]

Summary

Conclusions

The clinical features of CdLS vary widely among patients, ranging from the classic form, which is severe, to mild forms and including some individuals who have non-syndromic phenotypes but some form of mental retardation [17]. Mutations in the SMC3 and SMC1A genes occur in patients with a mild CdLS clinical presentation, including mild facial structural anomalies, no absence or reduction of limbs or digits, no other major structural anomalies or, in some instances, mild to moderate mental retardation with a non-syndromic phenotype [9]. The single-nucleotide deletion (c.516delT) in exon 10 described here is, according to information available in the Human Genome Mutation Database [19] and, to the best of our knowledge, a novel heterozygous mutation in the NIPBL gene. A copy of the written consent is available for review by the Editor-in-Chief of this journal

Introduction

Discussion

Findings

16. Hirano T: At the heart of the chromosome