Clinical utility of the ABCR400 microarray: basing a genetic service on a commercial gene chip.
OBJECTIVE
To assess the clinical utility of ABCR400 microarray testing in patients with ABCA4-associated retinopathies and to report on possible issues that could arise should genetic results be delivered without validation.


METHODS
One hundred thirty-two probands were genotyped with the microarray. Diagnostic assays were designed to verify all mutations identified in individuals in whom at least 2 causative mutations were found. Mutations were verified in the probands, and wherever possible cosegregation analysis was performed in additional family members.


RESULTS
Eighty-five of the 132 probands (64.4%) genotyped with the microarray had 2 or more disease-associated mutations identified. Verification of the genotyping, however, resulted in only 80 families being able to benefit from genetic result delivery. The remaining families could not receive results owing to the confounding effect of multiple ABCA4 mutations or the incorrect identification of mutations.


CONCLUSIONS
The ABCR400 microarray is useful for mutation screening; however, raw data cannot be delivered directly to patients. All mutations should be verified and, whenever possible, investigated in other family members.


CONCLUSIONS
Validated ABCR400 results provide an unequivocal molecular diagnosis, allowing family members to be offered diagnostic, predictive, carrier, and prenatal testing. Use of the microarray can inform decision-making and identify candidates for future therapies.
Roberts
Lisa J
LJ
University of Cape Town/Medical Research Council Human Genetics Unit, Division of Human Genetics, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa. lisa.roberts@uct.ac.za
Ramesar
Rajkumar S
RS
Greenberg
Jacquie
J
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D033142:Genetic Services; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010375:Pedigree; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000235:genetics*; D018570:Risk Assessment
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters