%0 Journal Article
%T Custom CGH array profiling of copy number variations (CNVs) on chromosome 6p21.32 (HLA locus) in patients with venous malformations associated with multiple sclerosis
%A Alessandra Ferlini
%A Matteo Bovolenta
%A Marcella Neri
%A Francesca Gualandi
%A Alessandra Balboni
%A Anton Yuryev
%A Fabrizio Salvi
%A Donato Gemmati
%A Alberto Liboni
%A Paolo Zamboni
%J BMC Medical Genetics
%D 2010
%I BioMed Central
%R 10.1186/1471-2350-11-64
%X In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999 bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate.In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r = 0.6590, p = 0.0104; linear regression analysis r = 0.6577, p = 0.0106).The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype.The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.Although multiple sclerosis is the most prevalent neurological disease in the young adult population, it is catalogued as a neurodegenerative disorder of unknown aetiology [1]. Indeed, despite the proposal of inflammatory, infective, and autoimmune factors as pathogenic agents in this disease, their links with its a
%U http://www.biomedcentral.com/1471-2350/11/64