Impact of genotype-first diagnosis: the detection of microdeletion and microduplication syndromes with cancer predisposition by aCGH

被引:29
作者
Adams, Sara Anne [1 ]
Coppinger, Justine [1 ]
Saitta, Sulagna C. [2 ]
Stroud, Tracy [3 ]
Kandamurugu, Manikum [4 ]
Fan, Zheng [4 ]
Ballif, Blake C. [1 ]
Shaffer, Lisa G. [1 ,5 ]
Bejjani, Bassem A. [1 ,6 ,7 ]
机构
[1] Signature Genom Labs LLC, Spokane, WA 99207 USA
[2] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA
[3] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Columbia, MO USA
[4] Univ N Carolina, Div Pediat Genet & Metab, Chapel Hill, NC USA
[5] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA
[6] Washington State Univ, WWAMI Med Educ Program, Pullman, WA 99164 USA
[7] Sacred Heart Med Ctr, Spokane, WA USA
关键词
array CGH; comparative genomic hybridization; cancer; predisposition testing; mental retardation; MENTAL-RETARDATION; DISCOVERY; POLYPOSIS; DELETION; GENE;
D O I
10.1097/GIM.0b013e3181a028a5
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. Genet Med 2009:11(5):314-322.
引用
收藏
页码:314 / 322
页数:9
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