Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group.
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.
Ali
Abdullah Mahmood
AM
Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Kirby
Michelle
M
Jansen
Michael
M
Lach
Francis P
FP
Schulte
Jennifer
J
Singh
Thiyam Ramsing
TR
Batish
Sat D
SD
Auerbach
Arleen D
AD
Williams
David A
DA
Meetei
Amom Ruhikanta
AR
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
C499908:FANCL protein, human; D052240:Fanconi Anemia Complementation Group L Protein