Az első hazai tapasztalatok összegzése kromoszomális microarray-analízis és teljesexom-szekvenálás módszerekkel a magzati diagnosztikában

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Introduction: One of the major technological innovations of the last decade has been the proliferation of high-throughput molecular genetic testing methods, such as chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in prenatal diagnostics. Objective: Over the past 5 years, our working group has performed more than 252 prenatal examinations, indicated by ultrasound abnormalities of varying severity. Depending on the results of classical cytogenetic studies, we performed high-resolution CMA and WES analyses, with the aim to map the proportion of excess genetic information in the Hungarian population, as described in the literature. Method: CMA studies were performed using the “GeneChip System 3000 Instrument” platform with SNP-based comparative hybridization. We also performed next-generation sequencing of the whole human exome using IonTorrent and Illumina platforms. Results: A total of 252 fetal CMA examinations were performed and 42% showed some loss or gain, of which 22% showed pathogenic abnormalities. We performed WES in 42 CMA-negative cases, of which 9 (21.4%) were identified as pathogenic abnormalities supporting the inheritance process, with presumed association with fetal phenotype, based on the ClinVar database or ACMG classification. Discussion: Given the indirect nature of fetal phenotype assessment, prenatal CMA and WES analysis should be limited primarily to genes and chromosomal regions associated with ultrasound-identifiable symptoms. Parental examination is of paramount importance in both CMA and WES analyses, especially in cases where the resulting disorder cannot be clearly associated with ultrasound abnormalities. Conclusion: It is important to define the parameters by which copy number variations are detected in fetal samples. Recommendations for reporting variants confirmed by WES testing should also be given (taking international recommendations into account). These will provide more useful information for prenatal clinical genetic counselling. Orv Hetil. 2024; 165(14): 523–530.

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