Genomic coordinate 9:95,099,054
Here I present: “Fanconi Anemia”, Victor McKusick, Mendelian Inheritance in Man’, 1966. (FANCC) icd10=D61.03
INTRODUCTION.
Fanconi anemia is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of Fanconi anemia is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair.
Fanconi anemia is an inherited genetic disorder that affects the bone marrow, leading to decreased production of all types of blood cells (pancytopenia). It also causes physical abnormalities, organ defects, and a greatly increased risk of certain cancers.
CAUSE:
Genetic: Autosomal recessive (most cases) or X-linked recessive.
Mutations: In one of over 20 known genes (e.g., FANCA, FANCC, FANCG).
These genes are involved in DNA repair, especially fixing DNA crosslinks.
Defective DNA repair → genomic instability → cell death and cancer risk.
MAJOR FEATURES.
1. Bone Marrow Failure
Usually appears in childhood.
Leads to:
Anemia (low red cells → fatigue, pallor)
Leukopenia (low white cells → infections)
Thrombocytopenia (low platelets → bleeding, bruising)
2. Physical Abnormalities (in ~60–75% of patients)
Short stature.
Abnormal thumbs (absent, hypoplastic).
Skin pigmentation (café-au-lait spots, hypopigmentation).
Microcephaly and small eyes.
Renal or urinary tract anomalies.
Skeletal, cardiac, or GI defects.
3. CANCER PREDISPOSITION
Very high risk of:
Acute myeloid leukemia (AML).
Myelodysplastic syndrome (MDS)
Head, neck, or gynecologic squamous cell cancers.
There is evidence that Fanconi anemia can be caused by mutation in the FANCC (Fanconi anemia of complementation group-C) gene encoded on cytogenetic location 9q22.32 and genomic coordinate 9:95,099,054.
