Cornelia de Lange syndrome (CdLS;
http://www.ncbi.nlm.nih.gov/omim/122470), also known as Brachmann-de Lange syndrome, is a clinically and genetically heterogeneous developmental disorder characterized by growth and mental retardation [
1,
2]. The prevalence of mild and classic CdLS is estimated to be as high as 1.6 to 2.2/100,000 births [
3]. Growth retardation is an almost universal finding in patients with CdLS and typically has a pre-natal onset. Mental retardation in patients with CdLS is often severe, resulting in a mean IQ of 53 [
1]. Many patients also demonstrate autism-like behavior and self-injurious behavior [
4]. No gender-based predilection has been reported, and no differences linked to maternal age or race has been described [
3]. The majority of cases are sporadic, and very few familial cases of CdLS have been reported [
4]. Pedigree analyses of several families have demonstrated autosomal dominant inheritance with both maternal and paternal transmission [
5].
Multiple genes are considered to be responsible for CdLS, all of which are implicated in sister chromatid cohesion [
6]. Mutations in the
NIPBL gene on chromosome 5p13.1 account for approximately 50% of CdLS cases and have been shown to cause both mild and severe forms of the disease [
1]. The
NIPBL gene is 9.5 kbp in length and contains 47 exons that encode two isoforms of 2804 and 2697 amino acids, termed delangin-A and delangin-B, respectively [
1]. The human NIPBL proteins share homology with
Drosophila melanogaster Nipped-B and Scc2 from the budding yeast
Saccharomyces cerevisiae[
6]. The NIPBL protein is directly associated with chromatin while playing a role in the loading of the cohesin complex that mediates sister chromatid cohesion to chromosomes. It also has a dose-dependent gene-regulatory function [
7]. Furthermore, mutations in the
SMC1A gene cause an X-linked form of CdLS [
8]. Mutations in the
SMC3 gene on chromosome 10 have also been reported to cause CdLS [
9]. The
SMC1A and
SMC3 genes encode the two mitotic cohesion subunits [
10]. Cohesin plays a role in sister chromatid cohesion during mitosis and meiosis, in DNA repair and in gene expression [
11]. Evidence that cohesin regulates gene expression is accumulating rapidly [
12‐
14] and supports the hypothesis that developmental deficits in patients with CdLS likely arise from changes in cohesin-regulated gene expression that alter transcription in multiple ways [
15,
16]. Here, we report the first molecular analysis of the
NIPBL gene in an Iranian newborn baby diagnosed with CdLS.