title: Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group.
abstract: Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA crosslinking agents. Eight FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL and FANCM) and three non-FA proteins (FAAP100, FAAP24 and HES1) form an FA nuclear core complex, which is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. FANCL possesses a PHD/RING-finger domain and is a putative E3 ubiquitin ligase subunit of the core complex. In this study, we report an FA patient with an unusual presentation belonging to the FA-L complementation group. The patient lacks an obvious FA phenotype except for the presence of a café-au-lait spot, mild hypocellularity and a family history of leukemia. The molecular diagnosis and identification of the FA subgroup was achieved by FA complementation assay. We identified bi-allelic novel mutations in the FANCL gene and functionally characterized them. To the best of our knowledge, this is the second reported case belonging to the FA-L complementation group.
authors.affiliation: Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Abdullah Mahmood
authors.initials: AM
authors.lastname: Ali
authors.forename: Michelle
authors.initials: M
authors.lastname: Kirby
authors.forename: Michael
authors.initials: M
authors.lastname: Jansen
authors.forename: Francis P
authors.initials: FP
authors.lastname: Lach
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schulte
authors.forename: Thiyam Ramsing
authors.initials: TR
authors.lastname: Singh
authors.forename: Sat D
authors.initials: SD
authors.lastname: Batish
authors.forename: Arleen D
authors.initials: AD
authors.lastname: Auerbach
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: Amom Ruhikanta
authors.initials: AR
authors.lastname: Meetei
mesh_terms: D000483:Alleles; D019080:Cafe-au-Lait Spots; D005192:Family Health; D005199:Fanconi Anemia / Q000235:genetics*; D052240:Fanconi Anemia Complementation Group L Protein / Q000235:genetics*; D005816:Genetic Complementation Test; D006801:Humans; D007223:Infant; D007938:Leukemia; D008297:Male; D009154:Mutation
chemical_list: C499908:FANCL protein, human; D052240:Fanconi Anemia Complementation Group L Protein