Fine mapping of a putatively imprinted gene for familial non-chromaffin paragangliomas to chromosome 11q13.1: evidence for genetic heterogeneity.
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.
Mariman
E C
EC
Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
van Beersum
S E
SE
Cremers
C W
CW
Struycken
P M
PM
Ropers
H H
HH
D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005260:Female; D008040:Genetic Linkage; D018392:Genomic Imprinting; D006239:Haplotypes; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D010236:Paraganglioma, Extra-Adrenal / Q000235:genetics*; D010375:Pedigree