Impact of genotype-first diagnosis: the detection of microdeletion and microduplication syndromes with cancer predisposition by aCGH.
BACKGROUND
The use of microarray-based comparative genomic hybridization has allowed the genetic diagnosis of some conditions before their full clinical presentation. This "genotype-first" diagnosis has the most clinical implications for genomic alterations that confer an elevated risk of cancer. In these cases, diagnosis before the manifestation of the patient's full phenotype dramatically impacts genetic counseling, clinical management, and eventual prognosis and survivability.


METHODS
Using microarray-based comparative genomic hybridization, we tested 18,437 individuals with indications such as developmental disabilities and congenital anomalies.


RESULTS
We identified 34 (0.18%) individuals with DNA copy number gains or losses that encompassed gene regions associated with recognized genetic conditions with an increased risk for cancer. Three of the 34 individuals (8.8%) had a previously abnormal cytogenetic study which microarray-based comparative genomic hybridization confirmed and/or further characterized. Seven of the 34 individuals (20.6%) either had the correct disease specified in the clinical indication for study or had clinical features highly indicative of that syndrome. The remaining 24 patients (70.6%) had indications for study that were not specific to the diagnosed syndrome, such as "developmental delay" or "dysmorphic features."


CONCLUSIONS
The ability of microarray-based comparative genomic hybridization to rapidly and objectively interrogate the genome for chromosomal imbalances has led to the opportunity to optimize medical management and outcome. This has an even more profound impact and clinical utility in conditions associated with cancer predisposition syndromes.
Adams
Sara Anne
SA
Signature Genomic Laboratories, LLC, Spokane, Washington, USA.
Coppinger
Justine
J
Saitta
Sulagna C
SC
Stroud
Tracy
T
Kandamurugu
Manikum
M
Fan
Zheng
Z
Ballif
Blake C
BC
Shaffer
Lisa G
LG
Bejjani
Bassem A
BA
D002675:Child, Preschool; D055028:Comparative Genomic Hybridization / Q000379:methods / Q000706:statistics & numerical data*; D000013:Congenital Abnormalities / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D046228:Microarray Analysis / Q000379:methods; D009369:Neoplasms / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*