Application of comparative genomic hybridisation on microarrays in determining genetic causes of mental retardation

Ciljevi istraživanja: Cilj ovog istraživanja bio je otkrivanje genetičkih uzroka razvojnog zaostajanja aCGH metodom. Ustroj studije: Retrospektivno istraživanje genetičke etiologije razvojnog zaostajanja (RZ)/mentalne retardacije (MR). Ispitanici i metode: Ispitanici u ovom istraživanju su djeca, njih 8 (5 djevojčica i 3 dječaka), upućena s Klinike za pedijatriju Kliničkog bolničkog centra Osijek zbog kliničke slike koja upućuje na razvojno zaostajanje. Svim je pacijentima prvo napravljeno genetičko testiranje koje se sastoji od kariotipizacije i molekularno-genetičke analize za fragilni X sindrom. Inicijalno testiranje pokazalo je uredan nalaz u slučaju ispitanika 4, 5, 6 i 8 te patološki nalaz kod ispitanika 1, 2, 3 i 7. Idući korak u testiranju bila je analiza genoma aCGH metodom na platformi SurePrint G3 Human CGH Bundle, 8×60K (Agilent Technologies, Santa Clara, US), sofisticiranijom metodom od onih korištenih u prvotnom genetičkom testiranju. Rezultati: Analizom su dokazane kromosomske promjene kod 4 ispitanika (2 djevojčica i 2 dječaka), odnosno kod 50% ispitanika. Promjene su uočene na kromosomima 6, 16, 21 i X. Zaključak: aCGH metoda pokazala se izvrsnom metodom probira za pacijente s nerazjašnjenim ID/DD, ASD i MCA budući da otkriva submikroskopske promjene koje su najčešći uzrok navedenih poremećaja, a koje je nemoguće detektirati standardnom kariotipizacijom.Objectives: The objective of this study was to discover genetic causes of developmental delay using aCGH method. Study design: Retrospective study of genetic causes of developmental delay (DD)/mental retardation (MR). Participants and methods: 8 children (5 girls and 3 boys), evaluated at the Clinic of Paediatrics, University Hospital Center Osijek and referred for developmental delay, participated in the study. Genetic testing that included karyotyping and molecular-genetic analysis for fragile X syndrome was performed on all patients. Some of the patients (4, 5, 6 and 8) had normal results of the initial testing, and others (1, 2, 3 and 7) had not. More sophisticated testing using the aCGH method was additionally performed. The platform that was used is called SurePrint G3 Human CGH Bundle, 8×60K (Agilent Technologies, Santa Clara, US). Results: The analysis showed chromosomal changes in 4 patients (2 girls and 2 boys) or in 50% of patients. The changes were observed on chromosomes 6, 16, 21 and X. Conclusion: The study has shown that aCGH method is an optimal screening method for patients with unexplained ID/DD, ASD and MCA since it detects submicroscopic aberrations that are the most common cause of these disorders and which can not be detected by using standard karyotyping