TY - JOUR
T1 - Validation of fanconi anemia complementation group A assignment using molecular analysis
AU - Moghrabi, Nabil N.
AU - Johnson, Monique A.
AU - Yoshitomi, Marvin J.
AU - Zhu, Xiaoman
AU - Al-Dhalimy, Muhsen J.
AU - Olson, Susan B.
AU - Grompe, Markus
AU - Richards, C. Sue
PY - 2009/3
Y1 - 2009/3
N2 - Purpose: Fanconi anemia is a genetically heterogeneous chromosomal breakage disorder exhibiting a high degree of clinical variability Clinical diagn oses are confirmed by testing patient cells for increased sensitivity to crosslinking agents Fanconi anemia complementation group assignment, essential for efficient molecular diagnosis of the disease, had not been validated for clinical application before this study The purpose of this study was (1) confirmation of the accuracy of Fanconi anemia complementation group assignment to Group A (FANCA) and (2) development of a rapid mutation detection strategy that ensures the efficient capture of all FANCA mutations Methods: Using fibroblasts from 29 patients, diagnosis of Fanconi anemia and assignment to complementation Group A was made through breakage analysis studies FANCA coding and flanking sequences were analyzed using denaturing high pressure liquid chromatography, sequencing, and multiplex ligation-dependent probe amplification Patients in which two mutations were not identified were analyzed by cDNA sequencing Patients with no mutations were sequenced for mutations in FANCC, G, E, and F Results: Of the 56 putative mutant alleles studied, 89% had an identifiable FANCA pathogenic mutation Eight unique novel mutations were identified Conclusion: Complementation assignment to Group A was validated in a clinical laboratory setting using our FANCA rapid molecular testing strategy.
AB - Purpose: Fanconi anemia is a genetically heterogeneous chromosomal breakage disorder exhibiting a high degree of clinical variability Clinical diagn oses are confirmed by testing patient cells for increased sensitivity to crosslinking agents Fanconi anemia complementation group assignment, essential for efficient molecular diagnosis of the disease, had not been validated for clinical application before this study The purpose of this study was (1) confirmation of the accuracy of Fanconi anemia complementation group assignment to Group A (FANCA) and (2) development of a rapid mutation detection strategy that ensures the efficient capture of all FANCA mutations Methods: Using fibroblasts from 29 patients, diagnosis of Fanconi anemia and assignment to complementation Group A was made through breakage analysis studies FANCA coding and flanking sequences were analyzed using denaturing high pressure liquid chromatography, sequencing, and multiplex ligation-dependent probe amplification Patients in which two mutations were not identified were analyzed by cDNA sequencing Patients with no mutations were sequenced for mutations in FANCC, G, E, and F Results: Of the 56 putative mutant alleles studied, 89% had an identifiable FANCA pathogenic mutation Eight unique novel mutations were identified Conclusion: Complementation assignment to Group A was validated in a clinical laboratory setting using our FANCA rapid molecular testing strategy.
KW - Complementation group assignment
KW - FANCA
KW - Fanconi anemia
KW - Molecular FANCA testing
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U2 - 10.1097/GIM.0b013e318193ba67
DO - 10.1097/GIM.0b013e318193ba67
M3 - Article
C2 - 19367192
AN - SCOPUS:63449086355
SN - 1098-3600
VL - 11
SP - 183
EP - 192
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 3
ER -