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Fanconi anemia A due to a novel frameshift mutation in hotspot motifs: Lack of FANCA protein
Author(s) -
Balta Gunay,
de Winter Johan P.,
Kayserili Hulya,
Pronk Jan C.,
Pronk Jan C.,
Joenje Hans
Publication year - 2000
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 - 10.1002/1098-1004(200006)15:6<578::aid-humu12>3.0.co;2-q
Subject(s) - fanca , frameshift mutation , biology , genetics , fanconi anemia , exon , gene , dna repair
Homozygosity for a frameshift mutation at codon 1213 of FANCA gene was identified in a Turkish patient. Immunoprecipitation‐western blot analysis showed the complete absence of the FANCA protein band. This novel mutation, a deletion of T at position 3639 in exon 37 (3639delT), is responsible for the disease and causes premature termination of translation 32 aa downstream. The deletion is (i) the T residue of 2 overlapping TGAGGC and CCTG hot spot motifs, (ii) flanked by several direct repeats, (iii) surrounded by the highly GC rich region that have frequently been identified at the site of human DNA deletions. The patient is the third living child of a first degree cousin marriage. The major abnormalities of the patient at the age of 6 months were growth retardation, microcephaly, hypoplastic right thumb, distal displacements of both thumbs and pelvic displacement of left kidney. Hematological presentation of the disease started before the age of 4 years. Hum Mutat 15:578, 2000. © 2000 Wiley‐Liss, Inc.