title: Molecular genetic analysis of a family with a history of Hodgkin's disease and dyschondrosteosis.
abstract: We describe a family in which two sisters with the autosomal dominant skeletal dysplasia, Leri-Weill dyschondrosteosis (LWD), developed Hodgkin's disease (HD) in late adolescence. In a preliminary attempt to identify HD susceptibility gene(s), HLA-typing and linkage analysis were carried out in the family. Using HLA molecular typing, both sisters were found to have inherited a variant of the HD-susceptibility allele, DPB1*0301, known as DPB1*2001. Following a previous report of a constitutional chromosome translocation (t(2q;8p)) in a family with LWD, preliminary linkage studies were carried out using chromosome 2q and 8p molecular markers. Regions covered by 7/10 chromosome 2 markers and 4/8 chromosome 8 markers were excluded as the location of a candidate LWD gene. Given the rarity of LWD and HD, their simultaneous occurrence is unlikely to have been due to chance. We suggest that a mutation in the LWD gene itself, or a gene closely linked to it, perhaps acting with increased susceptibility to infection conferred by DPB1*2001, resulted in HD in the two sisters.
authors.affiliation: Department of Medical Genetics, St Marys Hospital, Manchester, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Gokhale
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.forename: D
authors.initials: D
authors.lastname: Crowther
authors.forename: P
authors.initials: P
authors.lastname: Woll
authors.forename: C J
authors.initials: CJ
authors.lastname: Watson
authors.forename: S P
authors.initials: SP
authors.lastname: Dearden
authors.forename: W D
authors.initials: WD
authors.lastname: Fergusson
authors.forename: R F
authors.initials: RF
authors.lastname: Stevens
authors.forename: G M
authors.initials: GM
authors.lastname: Taylor
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002889:Chromosomes, Human, Pair 2; D002898:Chromosomes, Human, Pair 8; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006682:HLA-DP Antigens / Q000032:analysis / Q000235:genetics; D059868:HLA-DP beta-Chains; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000145:classification / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000145:classification / Q000235:genetics; D006650:Histocompatibility Testing; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors
chemical_list: D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II