Clinical application of trio-based whole-exome sequencing in idiopathic generalized epilepsy.

PURPOSE: Idiopathic generalized epilepsies (IGEs) are a common group of genetic generalized epilepsies with high genetic heterogeneity and complex inheritance. However, the genetic basis is still largely unknown. This study aimed to explore the genetic etiologies in IGEs. METHODS: Trio-based whole-exome sequencing was performed in 60 cases with IGEs. The pathogenicity of candidate genetic variants was evaluated by the criteria of the American College of Medical Genetics and Genomics (ACMG), and the clinical causality was assessed by concordance between the observed phenotype and the reported phenotype. RESULTS: Seven candidate variants were detected in seven unrelated cases with IGE (11.7%, 7/60). According to ACMG, a de novo SLC2A1 (c.376C>T/p.Arg126Cys) variant identified in childhood absence epilepsy was evaluated as pathogenic with clinical concordance. Six variants were assessed to be uncertain significance by ACMG, but then considered causative after evaluation of clinical concordance. These variants included CLCN4 hemizygous variant (c.2044G>A/p.Glu682Lys) and IQSEC2 heterozygous variant (c.4315C>T/p.Pro1439Ser) in juvenile absence epilepsy, EFHC1 variant (c.1504C>T/p.Arg502Trp) and CACNA1H (c.589G>T/p.Ala197Ser) both with incomplete penetrance in juvenile myoclonic epilepsy, and GRIN2A variant (c.2011C>G/p.Gln671Glu) and GABRB1 variant (c.1075G>A/p.Val359Ile) both co-segregated with juvenile myoclonic epilepsy. Among them, GABRB1 was for the first time identified as potential novel causative gene for IGE. SIGNIFICANCE: Considering the genetic heterogeneity and complex inheritance of IGEs, a comprehensive evaluation combined the ACMG scoring and assessment of clinical concordance is suggested for the pathogenicity analysis of variants identified in clinical screening. GABRB1 is probably a novel causative gene for IGE, which warrants further studies.

[Analysis of mitochondrial DNA D-loop region mutation and its significance in human oncocytoma].

OBJECTIVE: To investigate the mutation in mitochondrial DNA displacement-loop (mtDNA D-loop) region in oncocytoma and its relationship with tumorigenesis and tumor development. METHODS: The mtDNA D-Loop region of 20 thyroid or renal oncocytomas and the adjacent normal tissues were amplified by PCR, and then sequenced. Five human fetal renal tissues were collected as matched controls. RESULTS: Among the 20 oncocytomas, 21 mutations which focused on hypervariable region I (HVI) were found in 7 tumor tissues and 1 normal tissue with the mutation rates of 35% and 5%, respectively. At the same time, 191 polymorphisms were found in the 20 cases. CONCLUSION: mtDNA D-loop region, especially HV I, is the mutational hotspot of oncocytomas, which may be closely related with mtDNA duplicating rate and the function of mitochondria.

Enhanced low-temperature NH3-SCR performance of Ce/TiO2 modified by Ho catalyst.

Holmium was used as a dopant to boost the low-temperature NH3-selective catalytic reduction (SCR) performance of Ce/TiO2 catalyst. It was ascertained that certain amount of Ho-doping species could exceedingly improve the low-temperature SCR activity under 60 000 h-1 of Ce/TiO2, accompanied with the improvement of tolerance to H2O and SO2 at 200°C. Characterization results manifested that Ho modification could not only result in inhibiting the growth of TiO2 crystals and the enlargement of specific surface area but also lead to the enhanced redox ability and the increased amount of surface-adsorbed substances, all of which could promote the low-temperature NH3-SCR performance of Ce/TiO2.

Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy.

Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.

[Biomechanical research in treating unstable Pilon fracture with anatomic plate of distal tibia].

OBJECTIVE: To investigate the mechanical characteristics of new anatomic plate of distal tibia from view of biomechanics. METHODS: Twelve fresh adult moist ankle specimens were randomly divided into four block groups (every group had 3 specimens), 3 tibial specimens as a normal control (normal group N), 9 specimens were resulted in unstable distal tibial Pilon fracture. Using steel plate fixation with a new anatomic distal tibial plate (group A), reconstruction plate (group B), clover plate (group C). Group B and group C as control group to test the remote axial compressive strength, remote axial stiffness, reversing biomechanical properties, contacted characteristics of the tibial astragaloid articular surface. RESULTS: The remote axial compressive strength, remote axial stiffness, reversing biomechanical properties, contacted characteristics of tibial astragaloid articular surface the in distal tibial Pilon fracture instability of group A were near normal group N (P>0.05). Group A was best than group B and C (P<0.05). CONCLUSION: The new anatomic plate of distal tibia was relatively strong, which can reach effective and stable fixation for unstable distal tibial Pilon fracture.