Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities, present in 60%-75% of affected individuals, include one or more of the following: short stature; abnormal skin pigmentation; malformations of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ears (and decreased hearing), heart, gastrointestinal system, central nervous system; hypogonadism; and developmental delay. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. By age 40 to 50 years, the estimated cumulative incidence of bone marrow failure is 90%; the incidence of hematologic malignancies (primarily acute myeloid leukemia) 10%-30%; and of nonhematologic malignancies (solid tumors, particularly of the head and neck, skin, GI tract, and genital tract) 25%-30%. [from GeneReviews, Fanconi Anemia, pubmed:20301575 2016.06.01]

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 FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011, pubmed:21568838). [From MIM:227650, 2016.05.26]

Fanconi anemia, complementation group L (FANCL) is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. [From UniProt, uniprot:Q9NW38 2016.06.01]

FANCL has been reported in a male patient who had developmental delay, a cafe-au-lait spot, mild hypocellularity, and a family history of leukemia; in this patient, compound heterozygous mutation in the FANCL gene were identified (Ali et al., 2009, pubmed:19405097). FANCL has also been reported in two unrelated infants presenting as multiple congenital anomalies reminiscent of VACTERL (MIM:192350) or VACTERL-H (MIM:276950). The first patient, born of consanguineous Moroccan parents, was noted to have radial hypoplasia and intrauterine growth retardation on prenatal ultrasound at 14 weeks' gestation. Later investigations showed tetralogy of Fallot, left kidney agenesis, right kidney hydronephrosis, and esophageal atresia. After birth, the patient showed hypertelorism, broad nasal root and puffy cheeks, and bilateral absence of the thumbs. The infant died two months later and the abnormalities were confirmed by postmortem examination. Family history included two previous fetuses with congenital malformations; data available for one in which the pregnancy had been terminated revealed similar features. In the second family, a female Dutch infant showed intrauterine growth retardation, hydrocephalus, facial dysmorphism with depressed nasal tip, microtia, microphthalmia, cleft palate, short neck, short forearms, radial club hands with absent thumbs, hypoplastic sacrum, and anal atresia with rectovaginal fistula. She also had cardiac defects and renal hypoplasia. She died at age 2 days. Cells derived from both patients showed increased chromosomal breakage with diepoxybutane (DEB) or mitomycin C (MMC), consistent with a diagnosis of Fanconi anemia. A different homozygous truncating mutation in the FANCL gene was identified in each patient. (Vetro et al., 2015, pubmed:25754594).[From MIM:614083, 2016.06.01]

Ortholog of human FANCL (1 Drosophila to 1 human).

Dmel\Fancl shares 23% identity and 40% similarity with human FANCL.