Overgrowth Syndrome with 9q22.3 Microdeletion Detected by Microarray Comparative Genomic Hybridization

Microdeletion of 9q22.3 is a rare chromosomal disorder characterized by body overgrowth, facial dysmorphic features and psychomotor delay. The presence of genomic microdeletion or microdu-plication can not be identified by the conventional chromosomal analysis. Microarray comparative genomic hybridization (CGH) is a newly developed molecular cytogenetic technique that enables the identification of minute copy number variation (CNV) in the human genome. Here, we report a case of microdeletion in the 9q22.31-q22.33 region, which included a patched homolog 1 (PTCH1) gene, as detected by CGH and confirmed by fluorescence in situ hybridization (FISH) analyses in a neonate with prenatal onset of macrosomia, dysmorphism, and muscle hypotonia. To the best of our knowledge, this is the first case report of 9q22.3 microdeletion detected by CGH in Korea.

Rapid prenatal diagnosis for chromosomal aneuploidy using cDNA microarray-based comparative genomic hybridization / 대한산부인과학회지

OBJECTIVE: Prenatal cytogenetic diagnosis is limited to metaphase karyotype analysis of cultured cells obtained by amniocentesis or chorionic villus sampling. Moreover, genome wide analysis cannot be performed by FISH analysis using specific probe. Array comparative genomic hybridization (CGH) offers a number of advantages over conventional cytogenetic analysis and FISH. Microarray CGH can be highly comprehensive, amenable to very high resolution, sensitive and fast. The objective of this study was to determine the clinical use of cDNA microarray CGH for detection of fetal aneuploidy. METHODS: 21 amniotic fluid samples and 6 chorionic villi samples were obtained from 27 pregnant women in 9-19 gestational weeks. Genomic DNA was extracted from each sample and amplified. For cDNA microarray CGH analysis, test DNA sample and reference DNA sample were labeled with Cy3-dUTP and Cy5-dUTP, respectively. Each sample of labeled test and reference DNA was hybridized to microarray. The result was analysed with axon scanner and compared with cytogenetic analysis and FISH. RESULTS: In 27 cases, 3 cases with trisomy 21 and 1 case with trisomy 18 had increased hybridization signals on chromosome 21 and chromosome 18. One case with 45,X had decreased signals on chromosome X. One case with 46,X,i(Xq) had decreased signal on short arm of chromosome X and increased signal on long arm. And one case with 47,XYY had two fold increased signal on Y chromosome. cDNA microarray based CGH correctly identified fetal aneuploidy in all of the 7 cases with aneuploid fetuses. CONCLUSION: Prenatal genetic diagnosis by cDNA microarray-based CGH is an useful, innovative, rapid and accurate method. It is promising technique allowing rapid screening for whole chromosomal changes including aneuploidy, and may augment standard karyotyping techniques for prenatal genetic diagnosis by providing additional molecular information. This method may aid the discovery and description of minor genetic aberration, potentially enhancing future prenatal genetic diagnostic application.