High Resolution Copy Number Variant Analysis in Sturge-Weber Syndrome

Abstract

Purpose: : Sturge-Weber (SW) syndrome is a rare, sporadic, neurocutaneous disorder characterized by ipsilateral facial port-wine stain in the ophthalmic distribution of the trigeminal nerve, glaucoma with vascular eye abnormalities, and occipital leptomeningeal hemangioma. Chromosomal abnormalities such as the paracentric inversion of chromosome 4q and trisomy 10 have been noted in fibroblast cultures from regions affected with port-wine stains, and linkage analysis has linked familial capillary malformations to locus 5q11-23. The purpose of this study was to investigate the presence of DNA copy number changes by microarray comparative genomic hybridization (aCGH) in SW patients.

Methods: : Following IRB approval, informed consent was obtained from 3 SW patients. Subject genomic DNA derived from blood and 1 control Centre d'Etude du Polymorphisme Humain DNA sample were used in the array hybridizations.NimbleGen Human CGH 2.1M Whole Genome Tiling v2.0D microarray hybridization and scanning were performed. The raw data were normalized using NimbleScan software (Roche), and processed using the built-in rank segmentation algorithm in copy number software (Nexus). Areas of common aberration and genes in these regions were identified. Annotation and gene-GO term enrichment analysis was performed with DAVID (http://david.abcc.ncifcrf.gov/) to highlight the most relevant GO terms associated with the identified gene list.

Results: : The 3 subjects had 37 common regions of duplications/deletions. Of these, 28 areas showed gains; whereas 9 showed losses. Forty three genes were identified. Seven regions of duplications/deletions were novel. Two deletion regions have been reported in patients with mental retardation. Significant gene ontologic biological processes included neurologic system process and signal transduction.

Keywords: gene microarray • tumors