Molecular genetic analysis of a family with a history of Hodgkin's disease and dyschondrosteosis

Leukemia. 1995 May;9(5):826-33.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Chromosomes, Human, Pair 2
  • Chromosomes, Human, Pair 8
  • Family Health
  • Female
  • Genetic Linkage
  • HLA-DP Antigens / analysis
  • HLA-DP Antigens / genetics
  • HLA-DP beta-Chains
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class I / classification
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class II / analysis
  • Histocompatibility Antigens Class II / classification
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Testing
  • Hodgkin Disease / genetics*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Osteochondrodysplasias / genetics*
  • Pedigree
  • Risk Factors

Substances

  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II