This report describes ovarian dysgenesis (postulated), BRCA2-related.
In an investigation of a family with two cases of XX gonadal dysgenesis, both affected individuals were compound heterozygous for mutations in BRCA2. Both had levels of BRCA2 mRNA and protein significantly lower than family members heterozygous for one of these mutations, whose levels were also significantly lower than family members without any BRCA2 mutation. The human BRCA2 gene has been implicated in multiple types of cancer, including breast-ovarian cancer, Fanconi anemia, and Wilms tumor [MIM:600185].
There is a single orthologous gene in Drosophila, Dmel\Brca2, for which multiple RNAi targeting constructs, an amorphic allele, and several P-element insertion alleles have been generated. The human BRCA2 gene has not been introduced into flies.
Drosophila carrying a null allele of Brca2 are viable, but sterile. Both ovaries and testes are undersized, with ovaries showing widespread death of mid-stage egg chambers, and testes lacking the elongation, individualization, and coiling stages of spermatogenesis.
[updated May 2019 by FlyBase; FBrf0222196]
Hypergonadotropic ovarian failure is a heterogeneous disorder that, in the most severe forms, is a result of ovarian dysgenesis. Ovarian dysgenesis accounts for about half the cases of primary amenorrhea (pubmed:12836721). [from MIM:233300; 2019.05.06]
Assessment of RAD51-positive foci in fibroblast DNA, which is evidence of BRCA2 repairing double-stranded DNA breaks, was lower in one of the affected individuals than unaffected family members and unrelated controls. (Weinberg-Shukron et al. 2018, FBrf0240072)
BRCA2 functions during homologous recombination to control RAD51, a protein that catalyzes homologous pairing and DNA strand exchange. By physically interacting with both RAD51 and single-stranded DNA, BRCA2 mediates delivery of RAD51 preferentially to sites of ssDNA exposed as a result of DNA damage or replication problems. Through its action, BRCA2 helps restore and maintain integrity of the genome. (Holloman 2011, pubmed:21731065)
One human gene to one Drosophila gene.
Single, low-scoring ortholog of BRCA2.
