title: Heterozygote FANCD2 mutations associated with childhood T Cell ALL and testicular seminoma.
abstract: Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities characterised by cellular cross linker hypersensitivity. FA is caused by mutations in any of so far 15 identified FANC genes, which encode proteins that interact in a common DNA damage response (DDR) pathway. Individuals with FA have a high risk of developing acute myeloid leukaemia (AML) and squamous cell carcinoma. An increased cancer risk has been firmly established for carriers of mutations in FANCD1/BRCA2, FANCJ/BRIP1, FANCN/PALB2, RAD51C/FANCO and link the FA pathway to inherited breast and ovarian cancer. We describe a pedigree with FANCD2 mutations c.458T > C (p.Leu153Ser) and c.2715 + 1G > A (p.Glu906LeufsX4) with mild phenotype FA in the index case, T cell ALL in the Leu153Ser heterozygous brother and testicular seminoma in the p.Glu906LeufsX4 heterozygous father. Both FANCD2 alleles were present in the T Cell ALL and the seminoma. This links specific FANCD2 mutations to T cell ALL and seminoma without evidence of allelic loss in the tumour tissue.
authors: Department of Clinical Genetics and Human Genetics, University Medical Centre, Free University of Amsterdam, Amsterdam, The Netherlands.
authors: Stephanie
authors: S
authors: Smetsers
authors: Joanne
authors: J
authors: Muter
authors: Claire
authors: C
authors: Bristow
authors: Leena
authors: L
authors: Patel
authors: Kate
authors: K
authors: Chandler
authors: Denise
authors: D
authors: Bonney
authors: Robert F
authors: RF
authors: Wynn
authors: Anthony D
authors: AD
authors: Whetton
authors: Andrew M
authors: AM
authors: Will
authors: Davy
authors: D
authors: Rockx
authors: Hans
authors: H
authors: Joenje
authors: Gordon
authors: G
authors: Strathdee
authors: Jonathan
authors: J
authors: Shanks
authors: Eva
authors: E
authors: Klopocki
authors: Johan J P
authors: JJ
authors: Gille
authors: Josephine
authors: J
authors: Dorsman
authors: Stefan
authors: S
authors: Meyer
mesh_terms: D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000235:genetics; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009154:Mutation / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D018239:Seminoma / Q000235:genetics* / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein