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Identification and characterization of mutations in FANCL gene: A second case of Fanconi anemia belonging to FA‐L complementation group
Author(s) -
Ali Abdullah Mahmood,
Kirby Michelle,
Jansen Michael,
Lach Francis P.,
Schulte Jennifer,
Singh Thiyam Ramsing,
Batish Sat D.,
Auerbach Arleen D.,
Williams David A.,
Meetei Amom Ruhikanta
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21032
Subject(s) - fanconi anemia , fanca , biology , fancd2 , complementation , genetics , microbiology and biotechnology , gene , cancer research , phenotype , dna repair
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. © 2009 Wiley‐Liss, Inc.