Identification of genetic loci for basal cell nevus syndrome and inflammatory bowel disease in a single large pedigree

Carolien I. Panhuysen, Amir Karban, Alisa Knodle Manning, Theodore M. Bayless, Richard H. Duerr, Joan E. Bailey-Wilson, Ervin H. Epstein, Steven R. Brant

Research output: Contribution to journalArticlepeer-review

Abstract

Basal Cell Nevus Syndrome (BCNS) is an autosomal dominant disease. PTCH1 gene mutations have been found responsible in many but not all pedigrees. Inflammatory Bowel Disease (IBD) is a complex genetic disorder, disproportionate in Ashkenazim, and characterized by chronic intestinal inflammation. We revisited a large Ashkenazim pedigree, first reported in 1968, with multiple diagnoses of BCNS and IBD, and with a common genetic cause for both disorders proposed. We expanded the pedigree to four generations and performed a genome-wide linkage study for BCNS and IBD traits. Twelve members with BCNS, seven with IBD, five with both diagnoses and eight unaffected were genotyped. Both non-parametric (GENEHUNTER 2.1) and parametric (FASTLINK) linkage analyses were performed and a validation through simulation was performed. BCNS linked to chromosome 9q22 (D9S1120) just proximal to the PTCH1 gene (NPL = 3.26, P = 0.003; parametric two-point LOD = 2.4, parametric multipoint LOD = 3.7). Novel IBD linkage evidence was observed at chromosome 1p13 (D1S420, NPL 3.92, P = 0.0047; parametric two-point LOD = 1.9). Linkage evidence was also observed to previously reported IBD loci on 4q, (D4S2623, NPL 3.02, P = 0.012; parametric two-point LOD=2.15), 10q23 (D10S1225 near DLG5, NPL 3.33, P = 0.0085; parametric two-point LOD=1.3), 12 overlapping the IBD2 locus (D12S313, NPL 2.6, P = 0.018; parametric two-point LOD = 1.52), and 7q (D7S510 and D7S3046, NPL 4.06, P = 0.0035; parametric two-point LOD = 2.18). In this pedigree affected by both BCNS and IBD, the two traits and their respective candidate genetic loci segregate independently; BCNS maps to the PTCH1 gene and IBD maps to several candidate regions, mostly overlapping previously observed IBD loci.

Original languageEnglish (US)
Pages (from-to)31-41
Number of pages11
JournalHuman genetics
Volume120
Issue number1
DOIs
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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