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Background: Malformations of cortical development comprise phenotypically heterogeneous conditions, and the diagnostic value of genetic testing in blood still remains to be elucidated. We used targeted gene sequencing to identify malformations of cortical development caused by germline mutations and characteristics associated with pathogenic mutations.Methods: A total of 81 patients with malformations of cortical development were included. Genomic DNA was isolated from peripheral blood. Ninety-six genes were assessed using a targeted next-generation sequencing panel. Single-nucleotide variants and exonic and chromosomal copy number variations were examined with our customized pipeline.Results: Genetic causes were identified from blood in 19 (23.5%) patients with malformations of cortical development; 14 patients had pathogenic or likely pathogenic single-nucleotide variants in seven genes, including DCX (n = 5), DEPDC5 (n = 2), PAFAH1B1 (n = 3), TUBA1A (n = 1), TUBA8 (n = 1), TUBB2B (n = 1), and TUBB3 (n = 1). Five patients had pathogenic copy number variations. Multifocal involvement of the lesion (tangential distribution, P < 0.001) and concurrent involvement of multiple structures such as the cortex, white matter, and ventricle (radial distribution, P = 0.003) were more commonly found in patients with identified genetic causes. Intellectual disability was also more commonly associated with pathogenic mutations (P = 0.048). In a multivariable regression analysis, both tangential and radial radiological distribution of malformations of cortical development were independently associated with positive germline test results.Conclusion: We identified germline mutations in almost one-fourth of our patients with malformations of cortical development by using targeted gene sequencing. Germline abnormalities were more likely found in patients who had multifocal malformations of cortical development. [ABSTRACT FROM AUTHOR]

Objective To evaluate the predictive efficacies including sensitivity and positive predictive value of the genetic risk prediction model BRCAPRO and the Myriad BRCA risk calculator in Korean ovarian cancer patients. Methods Individuals undergoing genetic testing for BRCA mutations from November 2010–August 2016 were recruited from the Department of Obstetrics and Gynecology at a single institute in Korea. The observed BRCA1 and BRCA2 mutation statuses were compared with the predicted carrier probabilities using BRCAPRO and the Myriad BRCA risk calculator. Results Two hundred thirty-two patients were recruited, of whom 99.1% (230/232) were of Korean ethnicity. Of the 232 individuals, 206 and 26 had ovarian and double primary breast/ovarian cancer, respectively. Thirty-six individuals had a family history of breast/ovarian cancer in first-degree relatives. Fifty-seven patients (24.6%) tested positive for BRCA mutation (41 BRCA1 , 16 BRCA2 ). The mean BRCAPRO and Myriad scores for all patients were 6.4% and 7.7%, respectively. The scores were significantly higher for patients with positive BRCA mutation status (29.0% vs. 6.1%, P < 0.001, 12.1% vs. 7.7%, P < 0.001, respectively). For all patients, the respective areas under the receiver operating characteristics curves were 0.720 and 0.747 for the BRCAPRO and Myriad models to predict the risk of carrying a BRCA mutation. Both models overestimated the mutation probability in patients with a family history of breast/ovarian cancer (1.55-fold and 1.50-fold, respectively) and underestimated the probability in patients without a family history (both, 0.54-fold). Conclusion BRCAPRO and Myriad seem to be acceptable risk assessment tools for determining the risk of carrying BRCA mutations in Korean ovarian cancer patients. [ABSTRACT FROM AUTHOR]