Fine mapping of a putatively imprinted gene for familial non-chromaffin paragangliomas to chromosome 11q13.1 : evidence for genetic heterogeneity

• Published in: Human genetics Vol. 95; no. 1; pp. 56 - 62
• Main Authors: MARIMAN, E. C. M, VAN BEERSUM, S. E. C, CREMERS, C. W. R. J, STRUYCKEN, P. M, ROPERS, H. H
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 1995; Berlin; New York, NY
• Subjects: Adult; Biological and medical sciences; Child; Chromosome Mapping; Chromosomes, Human, Pair 11; Female; Genetic Linkage; Genomic Imprinting; Haplotypes; Head and Neck Neoplasms - genetics; Humans; Male; Medical sciences; Neurology; Paraganglioma, Extra-Adrenal - genetics; Pedigree; Tumors of the nervous system. Phacomatoses; Genetic mapping; Human; Family study; C11-Chromosome; Chemodectoma
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/bf00225075

Autosomal, dominantly inherited, non-chromaffin paragangliomas are tumors of the head and neck region occurring with a frequency of 1:30,000. Genomic imprinting probably influences the expression of the disorder, because tumor development is limited to individuals who have inherited the trait from their father. By linkage analysis and haplotyping of a single large family in which the pattern of inheritance is consistent with genomic imprinting, we have mapped the gene to a 5 cM region of chromosome 11q13.1 between D11S956 and PYGM. A maximum lod score of 7.62 at theta = 0.0 was obtained for D11S480. This interval does not overlap with a recently assigned locus for glomus tumors in other families: 11q22.3-q23.3. Furthermore, analysis of a second family showing the imprinting phenomenon resulted in the exclusion of the 5 cM area as the location of the disease gene, whereas an indication for linkage was obtained (Z = +2.65) with markers from the distal locus. These observations argue for the presence of two distinct imprinted genes for glomus tumors on 11q. A model for tumor initiation and progression is presented based on all available information.