title: Identification of a novel BRCA1 nucleotide 4803delCC/c.4684delCC mutation and a nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in two Greenlandic Inuit families: implications for genetic screening of Greenlandic Inuit families with high risk for breast and/or ovarian cancer.
abstract: Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We have recently identified a Greenlandic Inuit BRCA1 nucleotide 234T>G/c.115T>G (p.Cys39Gly) founder mutation, which at that time was the only disease-causing BRCA1/BRCA2 mutation identified in this population. Here, we describe the identification of a novel disease-causing BRCA1 nucleotide 4803delCC/c.4684delCC mutation in a Greenlandic Inuit with ovarian cancer. The mutation introduces a frameshift and a premature stop at codon 1572. We have also identified a BRCA1 nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in another Greenlandic individual with ovarian cancer. This patient share a 1-2 Mb genomic fragment, containing the BRCA1 gene, with four Danish families harbouring the same mutation, suggesting that the 249T>A/c.130T>A (p.Cys44Ser) mutation originates from a Danish ancestor. We conclude that screening of Greenlandic Inuits with high risk of breast or ovarian cancer should include sequencing of the entire BRCA1 gene.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. tvoh@rh.dk
authors.forename: Thomas V O
authors.initials: TV
authors.lastname: Hansen
authors.forename: Lars
authors.initials: L
authors.lastname: Jønson
authors.forename: Anders
authors.initials: A
authors.lastname: Albrechtsen
authors.forename: Ane Y
authors.initials: AY
authors.lastname: Steffensen
authors.forename: Eva
authors.initials: E
authors.lastname: Bergsten
authors.forename: Torben
authors.initials: T
authors.lastname: Myrhøj
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006116:Greenland; D040941:Heredity; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree; D018570:Risk Assessment; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D018389:Codon, Nonsense