两例父源性17q12微缺失综合征胎儿的产前诊断和遗传学分析

目的探讨两例父源性17q12微缺失综合征胎儿的产前诊断和遗传咨询。方法一名孕妇的两例胎儿的孕中晚期超声检查均提示肾脏异常和羊水过多,应用单核苷酸多态性分析(single nucleotide polymorphism array,SNP-array)分别对第1胎的脐血样本和第2胎的羊水样本进行产前诊断。发现第1胎染色体17q12微缺失后,父母进行外周血SNP-array检测以确定遗传来源。结合双亲临床病史,其父亲进行泌尿系统相关的565个基因的高通量测序,以排除泌尿系统及生殖器官先天性结构畸形相关的已知致病变异或疑似致病变异可能。结果该家系两例胎儿SNP-array结果均为arr[hg19]17q12(34822465~36243365)×1,大小约1.4 Mb,为17q12微缺失综合征,遗传自父亲。胎儿父亲未发现泌尿系统相关的致病或疑似致病变异。结论父源性17q12微缺失可能为两例胎儿超声肾脏异常和羊水过多的遗传学病因。产前SNP-array检测可明确诊断,为该家系的遗传咨询及产前诊断提供依据。     

Genetic polymorphisms for BDNF,COMT, and APOE do not affect gait or ankle motor control in chronic stroke: A preliminary cross-sectional study

ABSTRACT

Background: Motor deficits after stroke are a primary cause of long-term disability. The extent of functional recovery may be influenced by genetic polymorphisms.

Objectives: Determine the effect of genetic polymorphisms for brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT), and apolipoprotein E (APOE) on walking speed, walking symmetry, and ankle motor control in individuals with chronic stroke.

Methods: 38 participants with chronic stroke were compared based upon genetic polymorphisms for BDNF (presence [MET group] or absence [VAL group] of a Met allele), COMT (presence [MET group] or absence [VAL group] of a Met allele), and APOE (presence [ε4+ group] of absence [ε4- group] of ε4 allele). Comfortable and maximal walking speed were measured with the 10-m walk test. Gait spatiotemporal symmetry was measured with the GAITRite electronic mat; symmetry ratios were calculated for step length, step time, swing time, and stance time. Ankle motor control was measured as the accuracy of performing an ankle tracking task.

Results: No significant differences were detected (p ≥ 0.11) between the BDNF, COMT, or APOE groups for any variables.

Conclusions: In these preliminary findings, genetic polymorphisms for BDNF, COMT, and APOE do not appear to affect walking speed, walking symmetry, or ankle motor performance in chronic stroke.     

Neurólise do tronco celíaco com o uso de agulha única versus agulha dupla no manejo da dor abdominal maligna: estudo randômico controlado

BackgroundComputerized tomography‐guided celiac plexus neurolysis has become almost a safe technique to alleviate abdominal malignancy pain. We compared the single needle technique with changing patients’ position and the double needle technique using posterior anterocrural approach.MethodsIn Double Needles Celiac Neurolysis Group (n = 17), we used two needles posterior anterocrural technique injecting 12.5 mL phenol 10% on each side in prone position. In Single Needle Celiac Neurolysis Group (n = 17), we used single needle posterior anterocrural approach. 25 mL of phenol 10% was injected from left side while patients were in left lateral position then turned to right side. The monitoring parameters were failure block rate and duration of patient positioning, technique time, Visual Analog Scale, complications (hypotension, diarrhea, vomiting, hemorrhage, neurological damage and infection) and rescue analgesia.ResultsThe failure block rate and duration of patient positioning significantly increased in double needles celiac neurolysis vs. single needle celiac neurolysis (30.8% vs. 0.13.8±1.2 vs. 8.9 ± 1; p = 0.046, p ≤ 0.001 respectively). Also, the technique time increased significantly in double needles celiac neurolysis than single needle celiac neurolysis (24.5 ± 5.1 vs. 15.4 ± 1.8; p ≤ 0.001). No significant differences existed as regards visual analogue scale: double needles celiac neurolysis = 2 (0‐5), 2 (0‐4), 3 (0‐6), 3 (2‐6) and single needle celiac neurolysis = 3 (0‐5), 2 (0‐5), 2 (0‐4), 4 (2‐6) after 1 day, 1 week, 1 and 3 months respectively. However, visual analogue scale in each group reduced significantly compared with basal values (p ≤ 0.001). There were no statistically significant differences as regards rescue analgesia and complications (p > 0.05).ConclusionSingle needle celiac neurolysis with changing patients’ position has less failure block rate, less procedure time, shorter duration of patient positioning than double needles celiac neurolysis in abdominal malignancy.     

Improved pairwise kinship analysis using massively parallel sequencing

In the present study, 67 individuals from two families were analyzed to explore the efficacy of the ForenSeq^™ DNA Signature Prep Kit for pairwise kinship analysis. Six types of pairwise relationships including 81 parent-offspring, 60 full siblings, 48 grandparent-grandchildren, 147 uncle/aunt-nephew/nieces, 97 first cousins and 190 non-relatives were generated from these two families and the corresponding likelihood ratio (LR) was calculated using either sequence-based or length-based STR genotype data (i.e., LR_sequence and LR_length). In addition, 10,000 pairs of different relationships were simulated to estimate the system powers of the STRs and SNPs in this panel. The results showed that 54, 9 and 5 additional alleles were observed based on sequence for 27 autosomal STRs, 24 Y-STRs and 7 X-STRs, respectively, compared to those based on length information and 11 novel alleles were identified. Five mutations were found for 58 STRs in 81 parent-offspring but no mutations were observed for SNPs. For 27 autosomal STR loci, the LRs were increased from 9.20, 7.87, 2.01, 2.07, 0.42 for log₁₀LR_length to 11.52, 10.12, 2.61, 2.60, 0.52 for log₁₀LR_sequence for paternity index (PI), full siblings index (FSI), grandparent-grandchild index (GI), uncle/aunt-nephew/niece index (UNI) and first cousins index (FCI), respectively. PI values for 94 SNPs separated more than those of 27 STRs if two individuals were non parent-offspring relatives. For the simulation study, the effectiveness was 1 for the parent-offspring relationship at the thresholds of t₁ = − 4 and t₂ = 4 and was 0.9998 for full siblings (t₁ = − 2, t₂ = 2). With an error rate of 0.42%, 93.02% of second degree relatives could be identified at the thresholds of t₁ = − 1 and t₂ = 1. However, the effectiveness was only 0.4300 for first cousins with a relatively high error rate of 2.68% (t₁ = − 1, t₂ = 1). In conclusion, STR typing according to the sequence information is more polymorphic, which increases the discrimination power for kinship testing. Compared to these 27 STR markers, 94 SNP markers in this panel have advantages in paternity testing especially when mutated STRs are involved or when a relative is an alleged parent. This panel is powerful enough to resolve paternity and full sibling testing. Most of the second degree relationships could be identified with low error rate while more markers are still needed for first cousins testing.     

Microhaplotypes in forensic genetics

Microhaplotype loci (microhaps, MHs) are a novel type of molecular marker of less than 300 nucleotides, defined by two or more closely linked SNPs associated in multiple allelic combinations. The value of these markers is enhanced by massively parallel sequencing (MPS), which allows the sequencing of both parental haplotypes at each of the many multiplexed loci. This review describes the features of these multi-SNP markers and documents their value in forensic genetics, focusing on individualization, biogeographic ancestry inference, and mixture deconvolution. Foreseeable applications also include missing person identification, relationship testing, and medical diagnostic applications. The technique is not restricted to humans.