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Elevation-related weather developments control yeast co-occurrence system structure and also the plethora of keystone taxa about Mt. Norikura, Japan.
CONCLUSION The 46TT genetype, p.Glu502Lys and p.Gly542Ser variants of the F12 gene probably underlie the low FXII level in the proband. As shown by in vitro experiment, the p.Glu502Lys and p.Gly542Ser variants can both inhibit the synthesis and secrection of the FXII protein.OBJECTIVE To analyze the clinical phenotype of six pedigrees affected with osteogenesis imperfecta and their genetic basis. METHODS Peripheral blood or abortic tissues of the six pedigrees were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect pathological variants in the genome. Sanger sequencing was used for validating suspected variant among the six pedigrees and 100 healthy controls. RESULTS In pedigree 1, the proband and his daughter both carried a heterozygous c.1976G>C variant of COL1A1. The probands in pedigrees 2 to 6 respectively carried heterozygous variants of c.2224G>A of COL1A2, c.2533G>A of COL1A1, c.2845G>A of COL1A2, c.2532_2540del of COL1A1, and c.1847G>A of COL1A2. The same variants were not detected in their parents and the 100 healthy controls. CONCLUSION Variants of COL1A1/2 gene probably underlie the pathogenesis for osteogenesis imperfecta in these pedigrees. Discovery of the nevol variants has enriched the spectrum of COL1A1/2 gene variants and facilitated genetic counseling and prenatal diagnosis for the affected pedigrees.OBJECTIVE To identify pathogenic variants in two families with patients suspected for Joubert syndrome(UBST) by cerebellar vermis hypoplasia. METHODS Clinical data and peripheral venous blood and skin tissue samples were collected for the extraction of genomic DNA. Potential variants were screened by using targeted capture and next generation sequencing. Suspected variants were validated by PCR and Sanger sequencing. The frequency of the variants in the population was calculated. Pathogenicity of the variants was predicted by following the guidelines of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided to these families upon subsequent pregnancy. RESULTS The proband of family 1 was found to harbor homozygous c.2072delT (p.F691S*fs19) frameshift variant of the AHI1 gene, which may cause premature termination of translation of the Abelson helper integration site 1 after the 691st amino acid. The proband of family 2 was found to harbor compound heterozygous variants of the CPLANE1 gene, namely c.7243dupA (p.T2415Nfs*7) and c.8001delG (p.K2667Nfs*31), which can respectively lead to premature termination of translation of ciliogenesis and planar polarity effector 1 after the 2145th and 2667th amino acids. All of the three variants were previously unreported, and were predicted to be pathogenic by bioinformatic analysis. CONCLUSION The AHI1 c.2072delT and CPLANE1 c.7243dupA and c.8001delG variants probably underlay JBTS3 in family 1 and JBTS17 in family 2, respectively. Based on above results, prenatal diagnosis may be offered to the affected families upon their subsequent pregnancies.OBJECTIVE To explore the genetic basis for a consanguineous pedigree affected with inherited coagulation factor V deficiency. METHODS Genomic DNA was extracted from peripheral blood samples from the pedigree and subjected to next generation sequencing for screening variants of the F5 gene. Suspected pathogenic variant was verified by using Sanger sequencing. Pathogenicity of the variant was evaluated according to ACMG guidelines. RESULTS A homozygous frameshifting variant, c.4096delC (p.Leu1366Phefs*3), was identified in the F5 gene in the proband, which was confirmed to be derived from her consanguineous parents. This variant was absent in all databases including 10 000 in-house Chinese exome sequences. Based on the ACMG guidelines, the c.4096delC was predicted to be a pathogenic variant. CONCLUSION A novel pathogenic variant has been identified in the F5 gene in a consanguineous pedigree with inherited coagulation factor V deficiency, which has enriched the spectrum of F5 gene variants.OBJECTIVE To analyze the phenotype and genetic basis for a pedigree affected with hereditary coagulation factor XI deficiency. METHODS Activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), FXI activity (FXIC) and the antigen of FXI (FXIAg) were determined for the proband and members from his pedigree. Sanger sequencing was used to analyze all exons, exon-intronic boundaries, as well as the 5'- and 3'- untranslated regions of the F11 gene. Suspected variants were verified in her family members and confirmed by reverse sequencing. The impact of the variants on the protein function was predicted by using PolyPhen-2 and SIFT software. The protein structure and amino acid interaction were analyzed by using Swiss-PdbViewer. RESULTS The APTT, FXIC and FXIAg of the proband and her sister were significantly reduced to 73.0 s, 10.0%, 15.0% and 87.1 s, 2.0% and 11.5%, respectively. APTT of some family members was slightly prolonged, and FXIC and FXIAg also decreased to various extents. DNA sequencing revealed that the proband and her sister have carried compound heterozygous variants of c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) respectively in exons 7 and 9 of the F11 gene. Her father, sister and daughter were heterozygous for the c.738G>A (p.Trp228stop) variant, while her mother and nephew were heterozygous for the c.938G>T (p.Ser295Ile). Both PolyPhen-2 and SIFT predicted that the p.Ser295Ile variant is likely to be deleterious and can affect the protein function. Modeling analysis indicated that the p.Ser295Ile variant may lead to disruption of a hydrogen bond, resulting in alteration of protein structure and instability. CONCLUSION The compound heterozygous c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) variants of the F11 gene probably underlie the decreased FXI level in this pedigree.OBJECTIVE To detect pathological variant in a Chinese pedigree affected with congenital contractural arachnodactyly (CCA). METHODS Next generation sequencing (NGS) was used to scan the whole exome of the proband. Potential variant of the FBN2 gene was also detected in all members of the pedigree and 100 healthy controls by Sanger sequencing. With the determination of the genotype, prenatal diagnosis was carried out by amniotic fluid sampling. RESULTS A c.3528C>A (p.Asn1176Lys) variant was identified in the FBN2 gene of the proband, other patients from this pedigree, as well as the fetus. The same variant was not found among healthy members from this pedigree and the 100 healthy controls. CONCLUSION The c.3528C>A (p.Asn1176Lys) variant of the FBN2 gene probably underlies the pathogenesis of CCA in our case. The new variant has enriched pathological spectrum of the FBN2 gene.Central hypoventilation in adult patients is a rare life-threatening condition characterised by the loss of automatic breathing, more pronounced during sleep. In most cases, it is secondary to a brainstem lesion or to a primary pulmonary, cardiac or neuromuscular disease. More rarely, it can be a manifestation of congenital central hypoventilation syndrome (CCHS). We here describe a 25-year-old woman with severe central hypoventilation triggered by analgesics. Genetic analysis confirmed the diagnosis of adult-onset CCHS caused by a heterozygous de novo poly-alanine repeat expansion of the PHOX2B gene. She was treated with nocturnal non-invasive ventilation. We reviewed the literature and found 21 genetically confirmed adult-onset CCHS cases. Because of the risk of deleterious respiratory complications, adult-onset CCHS is an important differential diagnosis in patients with central hypoventilation.Strong evidence supports the involvement of sex steroid hormones in the development and progression of dementia. Attention has been largely focused on the association between genetic variants of estrogen receptor alpha (ERα, ESR1) with dementia, although several studies indicate that ERβ is predominantly expressed in the brain. Interestingly, however, a limited number of studies evaluate the role of ERβ (ESR2) in dementia. Therefore, a meta-analysis was conducted to clarify the association between ESR2 genetic polymorphisms and the risk of dementia. All the relevant studies evaluating ESR2 genetic polymorphisms and dementia were identified through online databases. In total, 14 studies including 20,609 subjects were analyzed. Collectively, it was found that a combined data set of ESR2 polymorphisms was not associated with dementia risk. Interestingly, ESR2 rs4986938 polymorphism is significantly associated with dementia in the Asian population (OR = 0.73, 95% CI 0.59-0.91, P = 0.006). The carrier of A allele in rs4986938 exhibits a protective effect against dementia (A vs. QX77 G, OR = 0.6633, P = 0.012; AA + GA vs. GG, OR = 0.6499, P = 0.014; GA vs. AA + GG, OR = 0.6672, P = 0.025; GA vs. GG, OR = 0.6617, P = 0.022). In conclusion, our study suggests that ESR2 genetic polymorphisms are not significantly associated with dementia risk. ESR2 rs4986938 may have potential as a genetic marker for dementia in the Asian population. However, further studies need to verify this conclusion.To date, only one study assessed quality of life (QoL) in patients with hereditary neuropathy with liability to pressure palsies (HNPP). We aimed to fill in this gap by investigating QoL in a cohort of patients with HNPP compared to Charcot-Marie-Tooth type 1A (CMT1A) patients, as well as to analyze sociodemographic and clinical features associated with QoL in HNPP. Eighteen genetically confirmed HNPP patients were age-and gender-matched with 18 CMT1A patients. SF-36 questionnaire was used to assess QoL. Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale Score (ONLS), Falls Efficacy Score (FES), Visual Analog Pain Scale, Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) were also used in our study. Although HNPP patients were less clinically impaired, no difference was observed in these two cohorts regarding SF-36 scores. Worse QoL in HNPP patients was associated with lower education (p  less then  0.01), physical work (p  less then  0.05), higher number of clinically affected nerves during the disease course (p  less then  0.01), worse MRC-SS score (p  less then  0.01), worse ONLS score (p  less then  0.01), and with more severe pain (p  less then  0.01), depression (p  less then  0.01), and fatigue (p  less then  0.01). Worse pain at the moment of testing appeared as a significant independent predictor of worse QoL in HNPP patients (β = - 0.93, p  less then  0.001). QoL was similarly impaired in patients with HNPP and patients with CMT1A. We identified different factors associated with QoL in HNPP, and many of these factors are amenable to treatment which is of special interest in these still incurable disease.PURPOSE To compare perinatal outcomes and to assess the predictors of birth weight (BW) after Roux-en-Y gastric bypass (RYGB) to those women unexposed to bariatric surgery. MATERIALS AND METHODS Singleton births from women submitted to RYGB (BSG) were matched to two control births by maternal age, delivery year, and gender. Control group 1 (CG1) and control group 2 (CG2) were selected according to the prepregnancy body mass index (BMI) less then  35 kg/m2 and ≥ 35 kg/m2, respectively, without previous bariatric surgery. RESULTS Fifty-eight pregnancies were evaluated in each group (n = 174). Neonates born after RYGB presented lower BW compared to CG1 (mean difference - 182.3 g; 95% CI - 333; - 31, P = 0.018) and CG2 (mean difference - 306.6 g, 95% CI - 502; - 111, P = 0.02). Although gestational age (GA) was similar (P = 0.219), fetal growth rate (in grams) per gestational week was higher in CG2 (β = 196.27, P  less then  0.001) vs. BSG (β = 127.65, P  less then  0.001), irrespective of gestational weight gain (GWG).
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