A de novo 2q35-q36.1 deletion incorporating IHH in a Chinese boy (47,XYY) with syndactyly, type III Waardenburg syndrome, and congenital heart disease

Abstract

Reports of terminal and interstitial deletions of the long arm of chromosome 2 are rare in the literature. Here, we present a case report concerning a Chinese boy with a 47,XYY karyotype and a de novo deletion comprising approximately 5 Mb between 2q35 and q36.1, along with syndactyly, type III Waardenburg syndrome, and congenital heart disease. High-resolution chromosome analysis to detect copy number variations was carried out using an Affymetrix microarray platform, and the genes affected by the patient's deletion, including IHH, were determined. However, no copy number changes were observed in his healthy parents. The present case exhibited novel syndactyly features, broadening the spectrum of clinical findings observed in individuals with 2q interstitial deletions. Our data, together with previous observations, suggest that IHH haploinsufficiency is the principal pathogenic factor in the syndactyly phenotype in this study, and that different types of variations at the IHH locus may cause divergent disease phenotypes. This is the first report of the involvement of IHH haploinsufficiency in syndactyly phenotype.

Biology of human melanocyte development, Piebaldism, and Waardenburg syndrome

“… Recently, IHH and EPHA4 haploinsufficiency have been suggested as the genes responsible for syndactyly and short stature associated with WS3, both lie in close proximity to PAX3 gene …”

PAX Genes in Cardiovascular Development

“…Sox10 , an SRY-box transcription factor, physically interacts with Pax3 [ 69 ] and mutations in both genes are known to be involved in Waardenburg syndrome in humans [ 70 ]. Patients typically present with NCC related defects such as hearing loss and pigmentation abnormalities, and in rare cases, also congenital heart abnormalities such as atrial and ventricular septal defects [ 71 , 72 ].…”

New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing

“…Copy number variation (CNV) is a new topic of increasing interest in genetic research. In addition, CNV has been reported to be associated with WS [ 8 – 10 ]. Recently, one study addressed the molecular etiology investigation of WS in individuals mostly from southeastern Brazil by sequential Sanger sequencing of all coding exons of the 6 WS-associated genes, followed by CNV detection by multiplex ligation-dependent probe amplification (MLPA) of the PAX3 , MITF , and SOX10 genes, and revealed novel pathogenic mutations [ 11 ].…”