title: Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia.
abstract: Fanconi anemia is an inherited disease characterized by bone marrow failure, congenital malformations, and predisposition to cancer. The breast cancer susceptibility gene BRCA2 was recently found to be associated with Fanconi anemia complementation group D1 (FA-D1). We examined four kindreds afflicted with Fanconi anemia for the presence of germline BRCA2 mutations. One kindred, of Ashkenazi Jewish ancestry, had five members who were diagnosed with breast cancer and two cousins who were BRCA2*6174delT/C3069X compound heterozygotes and had Fanconi anemia and brain tumors. In another kindred of Ashkenazi Jewish and Lithuanian Catholic ancestry, a child with Fanconi anemia and a medulloblastoma was a BRCA2*6174delT/886delGT compound heterozygote. Two other kindreds each contained a Fanconi anemia-afflicted child who developed medulloblastoma; one child was of Latin American ancestry and a compound heterozygote for BRCA2*I2490T/ 5301insA and the other was African American and a compound heterozygote for BRCA2*Q3066X/E1308X. Median age of the Fanconi anemia-afflicted children at brain tumor diagnosis was 3.5 years. The co-occurrence of brain tumors, Fanconi anemia, and breast cancer observed in one of these kindreds constitutes a new syndromic association. Individuals who carry a germline BRCA2 mutation and who plan to have children with a partner of Ashkenazi Jewish descent should consider undergoing genetic counseling.
authors.affiliation: Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. offitk@mskcc.org
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Orna
authors.initials: O
authors.lastname: Levran
authors.forename: Brian
authors.initials: B
authors.lastname: Mullaney
authors.forename: Katherine
authors.initials: K
authors.lastname: Mah
authors.forename: Khedoudja
authors.initials: K
authors.lastname: Nafa
authors.forename: Sat Dev
authors.initials: SD
authors.lastname: Batish
authors.forename: Raffaella
authors.initials: R
authors.lastname: Diotti
authors.forename: Hildegard
authors.initials: H
authors.lastname: Schneider
authors.forename: Amie
authors.initials: A
authors.lastname: Deffenbaugh
authors.forename: Thomas
authors.initials: T
authors.lastname: Scholl
authors.forename: Virginia K
authors.initials: VK
authors.lastname: Proud
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Nathan
authors.initials: N
authors.lastname: Ellis
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Arleen D
authors.initials: AD
authors.lastname: Auerbach
mesh_terms: D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008527:Medulloblastoma / Q000235:genetics; D010375:Pedigree; D012042:Registries; D013577:Syndrome