title: Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5.
abstract: Wilms tumor of the kidney occurs with increased frequency in association with two clinically and cytogenetically distinct congenital syndromes, the Wiedemann-Beckwith syndrome (WBS) and the triad of aniridia, genitourinary anomalies, and mental retardation (WAGR). Constitutional deletions in the latter situation and similar alterations in sporadic Wilms tumors have implicated the chromosomal 11p13 region in neoplastic development. In contrast, some sporadic cases of WBS have been reported to have a constitutional duplication of chromosome 11p15. In order to resolve this seeming paradox, we have analyzed a family segregating WBS for linkage to DNA markers mapped to chromosome 11p. Consonant with the cytogenetic alterations in sporadic WBS cases, we obtained evidence for tight linkage of the mutation causing the syndrome to markers located at 11p15.5. Also consistent with this localization, we identified a subset of Wilms tumors, not associated with WBS, which have attained somatic homozygosity through mitotic recombination, with the smallest shared region of overlap being distal to the beta-globin complex at 11p15.5. These data provide evidence that familial WBS likely results from a defect at the same genetic locus as does its sporadic counterpart. Further, the data suggest there is another locus, distinct from that involved in the WAGR syndrome, which plays a role in the association of Wilms tumor with WBS.
authors.affiliation: Ludwig Institute for Cancer Research, Royal Victoria Hospital, Montreal, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Koufos
authors.forename: P
authors.initials: P
authors.lastname: Grundy
authors.forename: K
authors.initials: K
authors.lastname: Morgan
authors.forename: K A
authors.initials: KA
authors.lastname: Aleck
authors.forename: T
authors.initials: T
authors.lastname: Hadro
authors.forename: B C
authors.initials: BC
authors.lastname: Lampkin
authors.forename: A
authors.initials: A
authors.lastname: Kalbakji
authors.forename: W K
authors.initials: WK
authors.lastname: Cavenee
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D009396:Wilms Tumor / Q000235:genetics*