Establishment And Application Of Genetic Diagnostic System For Eight Chromosome Microdeletion Syndromes By Fluorescence In Situ Hybridization

Objective: Chromosome microdeletion or microduplication syndromes are caused by deletion or duplication of small pieces of chromosome fragment, which are usually too small to be identified reliably by conventional cytogenetics. In this research, we aimed at 1) establishing clinical diagnostic norms of 8 common microdeletion syndromes for making preliminary diagnosis, 2) establishing a genetic diagnostic system for these syndromes by fluorescence in situ hybridization(FISH). By applying this system, patients could receive state of art informative genetic counseling, and prenatal diagnosis if necessary.Methods: Clinical diagnostic norms of 8 common microdeletion syndromes were established by employing the criteria and guidelines in clinical diagnosis of these syndromes, which were published by American College of Medical Genetics, American Academy of Pediatrics Committee on Genetics, and The Scientific and Research Advisory Committee of the Angelman Syndrome Foundation and correlated literatures. Preliminary diagnosis was made according to the norms. FISH diagnostic system was established on the basis of our previous work. And high-resolution cytogenetic analysis was used to exclude other chromosome abnormalities. The above diagnostic systems were applied to the diagnosis of 22qll deletion syndrome(22q11DS), Angelman syndrome(AS) and X-linked ichthyosis (XLI) respectively, one pedigree each.Results: Clinical diagnostic norms of 8 common microdeletion syndromes were established and applied to the routine clinical diagnosis. High-resolution cytogenetic analysis was normal in all patients and their parents. FISH test revealed that: 1) An interstitial 22q11 microdeletion was detected in the proband of 22q11DS pedigree, neither of his parents was carrier; 2) An interstitial 15q11 microdeletion was detected in the proband of AS pedigree, neither of his parents was carrier; and 3) An interstitial XP22.3 microdeletion was detected both in the proband and his mother of XLI pedigree, which means the mother is a carrier.Conclusion: Establishment of these clinical diagnostic norms and genetic diagnostic system made it possible to raise a preliminary clinical diagnosis according to patients' phenotypes, which could be further confirmed by FISH test. By utilizing this system, we can provide accurate genetic counseling and risk assessment for patients. However, as most of those syndromes have complex genetic heterogeneities, for some patients with typical clinical features but negative FISH test results, further investigation should be applied.