Fanconi’s anemia
**Core Concept**
Fanconi's anemia is a rare genetic disorder characterized by congenital abnormalities, bone marrow failure, and an increased risk of cancer. It is an autosomal recessive disorder caused by mutations in the FANCA, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCO (RAD51C), FANCP (SLX4), FANCQ (ERCC4), FANCR (RAD51), FANCS (BRCA1), or FANCT (XRCC2) genes, which are involved in the repair of interstrand DNA crosslinks.
**Why the Correct Answer is Right**
Fanconi's anemia is caused by a defect in the Fanconi anemia complementation group, which is responsible for the repair of interstrand DNA crosslinks. This results in genomic instability, leading to bone marrow failure, congenital abnormalities, and an increased risk of cancer. The cells of individuals with Fanconi's anemia exhibit a characteristic hypersensitivity to cross-linking agents such as mitomycin C and diephosphonacetic acid.
**Why Each Wrong Option is Incorrect**
**Option A:** Not applicable, as Fanconi's anemia is not caused by a defect in the immune system.
**Option B:** Ataxia-telangiectasia is a separate genetic disorder caused by mutations in the ATM gene, which is involved in the repair of double-strand breaks, not interstrand DNA crosslinks.
**Option C:** Bloom syndrome is a genetic disorder caused by mutations in the BLM gene, which is involved in the repair of DNA replication forks, not interstrand DNA crosslinks.
**Option D:** Not applicable, as Fanconi's anemia is not caused by a defect in the nervous system.
**Clinical Pearl / High-Yield Fact**
Fanconi's anemia is often associated with congenital abnormalities such as short stature, microcephaly, and abnormalities of the thumbs and toes. Patients with Fanconi's anemia are also at an increased risk of developing acute myeloid leukemia and other cancers.
**Correct Answer:** A.