Repositioning the hereditary paraganglioma critical region on chromosome band 11q23

摘要: Hereditary paragangliomas (PGL, glomus tumors, MIM no.168000) are mostly benign, slow-growing tumors of the head and neck region. The gene (or genes) affecting risk to PGL subject genomic imprinting: children affected fathers exhibit an autosomal dominant pattern disease inheritance, whereas mothers rarely if ever develop through maternal transmission. We previously confined approximately 6 Mb critical region on chromosome band 11q23 (PGL1). Based haplotype analysis extended Dutch pedigree, a 2 sub-region between D11S938 D11S1885 was proposed as PGL1 interval. In this study, we excluded interval by two new single tandem repeat polymorphisms (STRP) contained therein. Instead, predicted non-overlapping, more proximal D11S1647 D11S897, evaluated using nine STRP (D11S1986, five new, closely-linked STRP, D11S1347, D11S3178, D11S1987). Consistent with our prediction, observed substantial haplotype-sharing within pedigree. also analyzed four American families. A recombination event detected in one family further defined D11S1347 telomeric border. significant among three unrelated families, strongly suggesting that they originated from common ancestor. Thus, 1.5 D11S1986 showed identity-by-descent sharing for group