Among the 22 FA or FA-like genes, BRCA1 is considered as FANCS (Fanconi anemia gene), homozygous mutations of the BRCA1 gene contributed to FA group S. Mutations in at least 22 genes resulted in FA or FA-like phenotype, since proteins that produced from these genes are involved in DNA replication and repair. The likelihood of developing cancers in individuals with Fanconi anemia is between 10% and 30%, and studies showed that these individuals are hypersensitive to DNA crosslinking agents, such as mitomycin C and cisplatin. Other congenital abnormalities include malformed or absent kidneys, gastrointestinal abnormalities, heart defects, eye abnormalities and hearing loss. Meanwhile, 60% of the FA patients have physical abnormalities, such as short stature, microcephaly and a triangular face. About 90% of the FA patients have an impaired bone marrow function that leads to aplastic anemia, frequent infections and clotting problems. FA is a rare genetic disease with multi-organ disorder and patients usually have variable clinical presentations. It has a high incidence in individuals of Ashkenazi Jewish descent, the Roma population of Spain and the Afrikaner population of South Africans. FA occurs in 1 in 160,000-360,000 individuals worldwide. īRCA1 biallelic pathogenic mutations are extremely rare, which are regarded as embryonically lethal or causing Fanconi anemia (FA). BRCA1 mutations have also been linked to increase risk in cervical, esophagus, liver, stomach, and uterine cancers however, the increased risks ranged from one to four fold and the exact risk was inconsistent. Other studies reported that significant risk of melanoma and pancreatic cancer was observed in BRCA mutation carriers. Men with these mutations have an increased life time risk of breast cancer by 1% over male non-carriers, in addition to the risk of developing prostate carcinoma. ![]() ![]() Women carrying BRCA1 pathogenic variant have a significant life time risk of breast and ovarian cancers as high as 84%. BRCA1 also interacts with proteins such as MSH2 in the DNA mismatch repair mechanism, and, possibly, poly (ADP-ribose) polymerase (PARP) in the single-strand repair. BRCA1 functions in the DNA double-strand break repair by interacting with other proteins such as RAD51 in the repair process. Biallelic mutations in BRCA1 were considered to be lethal during embryonic development, which was consistent with the observation in BRCA1 homozygous knock-out mice models. At least one functional allele of BRCA1 is essential for human embryogenesis and development. Hereditary breast and ovarian cancer syndrome is an inherited cancer-predisposition syndrome and is predominantly caused by mutations in the BRCA1 or BRCA2 genes.
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