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IntroductionGenetic epilepsy is a large group of clinically and genetically heterogeneous neurological disorders characterized by recurrent seizures, which have a clear association with genetic defects. In this study, we have recruited seven families from China with neurodevelopmental abnormalities in which epilepsy was a predominant manifestation, aiming to elucidate the underlying causes and make a precise diagnosis for the cases.MethodsWhole-exome sequencing (WES) combined with Sanger sequencing was used to identify the causative variants associated with the diseases in addition to essential imaging and biomedical examination.ResultsA gross intragenic deletion detected in MFSD8 was investigated via gap-polymerase chain reaction (PCR), real-time quantitative PCR (qPCR), and mRNA sequence analysis. We identified 11 variants in seven genes (ALDH7A1, CDKL5, PCDH19, QARS1, POLG, GRIN2A, and MFSD8) responsible for genetic epilepsy in the seven families, respectively. A total of six variants (c.1408T>G in ALDH7A1, c.1994_1997del in CDKL5, c.794G>A in QARS1, c.2453C>T in GRIN2A, and c.217dup and c.863+995_998+1480del in MFSD8) have not yet been reported to be associated with diseases and were all evaluated to be pathogenic or likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines.MethodsBased on the molecular findings, we have associated the intragenic deletion in MFSD8 with the mutagenesis mechanism of Alu-mediated genomic rearrangements for the first time and provided genetic counseling, medical suggestions, and prenatal diagnosis for the families. In conclusion, molecular diagnosis is crucial to obtain improved medical outcomes and recurrence risk evaluation for genetic epilepsy.

Introduction: The HKαα (Hong Kong αα) allele containing both the -α(3.7) and ααα(anti4.2) is an unusual rearrangement of the α globin gene cluster. Currently, ααα(anti4.2) fragments cannot be detected through the routine thalassemia diagnostic kit. The genotype of -α(3.7)/αα, HKαα/-α(3.7) and HKαα/αα is entirely the result of -α(3.7)/αα by the gap-polymerase chain reaction (gap-PCR), which would cause some cases of the HKαα allele to be mistaken as -α(3.7)/αα. Methods: Genetic diagnosis was performed in 17166 cases, using single PCR and two-round nested PCR to detect the HKαα allele in 895 cases. It showed -α(3.7) and α2 bands by gap-PCR, and reverse dot-blot assays were performed to detect the non-deletional α thalassemia point mutations and β thalassemia point mutations. Results: The HKαα allele was found in 56 samples. The rates of HKαα/αα, HKαα/-α(3.7) and HKαα/--(SEA) were 4.92%, 0.67% and 0.67%. The rate of the HKαα allele was 0.33% in a southern Chinese population. In the HKαα/αα thalassemia group, the levels of hemoglobin (Hb), mean cell volume (MCV), and mean cell hemoglobin (MCH) were similar to the -α(3.7)/αα thalassemia group. The hematology of the HKαα/--(SEA) carriers was similar with the α(0) thalassemia carriers, and Hb is usually over 100 g/l. The two families carrying HKαα/--(SEA) genotype chose to retain the fetuses in our study. Conclusions: There was a certain proportion of the HKαα allele in southern Chinese population, and the hematologic manifestations were mild. Differential diagnosis of HKαα genotype from -α(3.7)/αα can provide more accurate genetic diagnosis and clinical thalassemia genetic counseling.