title: Copy number variations are not modifiers of phenotypic expression in a pair of identical twins carrying a BRCA1 mutation.
abstract: Mutations in BRCA1 and BRCA2 genes confer a high risk of breast and ovarian cancer but the incomplete penetrance of these mutations suggests that other genetic and/or environmental factors may modify this risk. We present a family where all affected members carried a mutation in the BRCA1 gene and the index case had suffered from cancer twice in the last 27 years, whereas her monozygotic twin sister, also a carrier of the mutation, remained healthy. As copy number variants (CNVs) contribute to phenotypic diversity, a comparative genomic hybridization array (CGH) was performed to see whether the differences in the CNV profile were a modifier factor of the phenotype in our monozygotic twins. Our results show that differences in the CNVs profile were not the cause of the extremely variable penetrance observed in our MZ twin. The search for an explanation should not therefore be limited to genetic changes at the level of the DNA sequence.
authors.affiliation: Genetics Department, Hospital Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lasa
authors.forename: T
authors.initials: T
authors.lastname: Ramón y Cajal
authors.forename: G
authors.initials: G
authors.lastname: Llort
authors.forename: J
authors.initials: J
authors.lastname: Suela
authors.forename: J C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: M
authors.initials: M
authors.lastname: Cornet
authors.forename: C
authors.initials: C
authors.lastname: Alonso
authors.forename: A
authors.initials: A
authors.lastname: Barnadas
authors.forename: M
authors.initials: M
authors.lastname: Baiget
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013030:Spain; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human