0
selected
-
1.
Progressive sector retinitis pigmentosa due to c.440G>T mutation in SAG in an Australian family.
Pappalardo, J, Heath Jeffery, RC, Thompson, JA, Charng, J, Chelva, ES, Constable, IJ, McLaren, TL, Lamey, TM, De Roach, JN, Chen, FK
Ophthalmic genetics. 2021;(1):62-70
Abstract
BACKGROUND Heterozygous c.440 G > T mutation in the S-antigen visual arrestin (SAG) gene has been described as a cause of autosomal dominant retinitis pigmentosa (adRP) in a series of patients of Hispanic origin. This study presents the early and late clinical features and disease progression rates in an Australian family with SAG adRP. MATERIALS AND METHODS An observational case series of four family members with adRP. They were examined clinically, with multi-modal retinal imaging and electroretinography (ERG) to ascertain phenotype. Disease progression rate was measured using optical coherence tomography (OCT) and fundus autofluorescence (FAF). A retinal dystrophy panel was used for the proband and cascade testing with targeted Sanger sequencing was conducted in other available family members. RESULTS The proband presented at 36 years of age with profoundly reduced full-field ERG responses despite a sector RP phenotype. This progressed to a classic RP pattern over several decades leaving a small residual island of central visual field. The horizontal span of the residual outer nuclear layer and the area of hyperautofluorescent ring contracted at a rate of 8-11% and 9-14% per year, respectively. DNA sequencing confirmed the segregation of SAG c.440 G > T mutation with disease. CONCLUSION SAG adRP presents with a reduced full-field ERG response consistent with a rod-cone dystrophy in mid-life despite a sector RP phenotype. Centripetal progression of the disease into the macula can be tracked by OCT and FAF imaging.
-
2.
The Significant Interaction of Excision Repair Cross-complementing Group 1 Genotypes and Smoking to Lung Cancer Risk.
Chen, LH, Shen, TC, Li, CH, Chiu, KL, Hsiau, YC, Wang, YC, Gong, CL, Wang, ZH, Chang, WS, Tsai, CW, et al
Cancer genomics & proteomics. 2020;(5):571-577
-
-
Free full text
-
Abstract
BACKGROUND The study aims to evaluate the contribution of excision repair cross-complementing group 1 (ERCC1), which plays an important role in genome integrity maintenance, to lung cancer risk. MATERIALS AND METHODS ERCC1 rs11615 and rs3212986 genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and their association with lung cancer risk was examined among 358 lung cancer patients and 716 controls. RESULTS The proportions of CC, CT and TT for the rs11615 genotype were 43.6%, 41.6% and 14.8% in the case group and 50.0%, 41.1% and 8.9% in the control group, respectively (p for trend=0.0082). Allelic analysis showed that ERCC1 rs11615 T-allele carriers have a 1.32-fold higher risk of lung cancer than wild-type C-allele carriers [95%confidence interval (CI)=1.09-1.60, p=0.0039]. In addition, a significant interaction between the rs11615 genotype and smoking status was observed. CONCLUSION The T allele of ERCC1 rs11615 jointly with smoking habits may contribute to a higher lung cancer risk in Taiwan.
-
3.
The relation of serum nesfatin-1 level with anthropometric and metabolic parameters in children and adolescents: A prospective observational study.
Kim, SH, Ahn, MB, Cho, WK, Cho, KS, Jung, MH, Suh, BK
Medicine. 2019;(19):e15460
-
-
Free full text
-
Abstract
Nesfatin-1, a recently discovered anorexigenic neuropeptide, seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis. The aim of this study was to evaluate the relation of serum nesfatin-1 level with metabolic and anthropometric parameters in children and adolescents.This study prospectively included 78 Korean children and adolescents (42 obese/overweight group and 36 healthy control group). Fasting serum nesfatin-1 was quantitatively assayed by ELISA. Lipid profile, fasting blood glucose, fasting insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as metabolic parameters.Serum nesfatin-1 levels were significantly lower in obese/overweight group than in control group (median 1.4 vs 2.0 ng/mL; P = .003). Pubertal subjects have the lower serum nesfatin-1 level than pre-pubertal subjects (median 1.5 vs 2.6 ng/mL; P = .02). Nesfatin-1 levels negatively correlated with chronological age (r = -0.37; P = .001), BMI (r = -0.33; P = .003), and BMI SDS (r = -0.26; P = .02).In conclusion, our results suggest that serum nesfatin-1 negatively correlated with BMI in children and adolescents. It suggests that nesfatin-1 might have an important role in regulation of food intake in obese children and adolescents.
-
4.
Spinal muscular atrophy with respiratory distress type 1: A multicenter retrospective study.
Viguier, A, Lauwers-Cances, V, Cintas, P, Manel, V, Peudenier, S, Desguerre, I, Quijano-Roy, S, Vanhulle, C, Fradin, M, Isapof, A, et al
Neuromuscular disorders : NMD. 2019;(2):114-126
Abstract
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder characterized by progressive motor and respiratory decline during the first year of life. Early and late-onset cases have recently been reported, although not meeting the established diagnostic criteria, these cases have been genotyped. We thus conducted a national multicenter observational retrospective study to determine the prognosis of children with SMARD1 according to their phenotype. We recorded all known French pediatric cases with mutations identified on the immunoglobulin μ-binding protein 2 gene and the presence of respiratory symptoms. Thirty centers provided 22 observations. A diaphragmatic palsy was diagnosed 1.5 months (p = 0.02) after first respiratory symptoms, and hypotonia preceded areflexia by 4 months (p = 0.02). Early onset of symptoms leading to specialist consultation before the age of 3 months was associated with a significantly worse prognosis (p < 0.01). Among the 6 patients who were still alive, all were tracheostomized. Only one case survived beyond 2 years without artificial ventilation. The remaining patients died at a median age of 7 months. Our results may help pediatricians to provide medical information to parents and improve the decision-making process of setting up life support.
-
5.
Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing.
Talundzic, E, Ndiaye, YD, Deme, AB, Olsen, C, Patel, DS, Biliya, S, Daniels, R, Vannberg, FO, Volkman, SK, Udhayakumar, V, et al
Antimicrobial agents and chemotherapy. 2017;(3)
-
-
Free full text
-
Abstract
The emergence of Plasmodium falciparum resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the P. falciparum kelch gene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms. The results were compared to previously reported Pfk13 polymorphisms from around the world. A total of 22 Pfk13 propeller domain polymorphisms were identified in this study, of which 12 have previously not been reported. Interestingly, of the 10 polymorphisms identified in the present study that were also previously reported, all had a different amino acid substitution at these codon positions. Most of the polymorphisms were present at low frequencies and were confined to single isolates, suggesting they are likely transient polymorphisms that are part of naturally evolving parasite populations. The results of this study underscore the need to identify potential drug resistance loci existing within a population, which may emerge under increasing drug pressure.
-
6.
Birth weight-for-gestational age is associated with DNA methylation at birth and in childhood.
Agha, G, Hajj, H, Rifas-Shiman, SL, Just, AC, Hivert, MF, Burris, HH, Lin, X, Litonjua, AA, Oken, E, DeMeo, DL, et al
Clinical epigenetics. 2016;:118
Abstract
BACKGROUND Both higher and lower fetal growth are associated with cardio-metabolic health later in life, suggesting that prenatal developmental programming determines long-term cardiovascular disease risk. Epigenetic mechanisms, which orchestrate fetal growth and development, may offer insight on the early programming of health and disease. We investigated whether birth weight-for-gestational is associated with DNA methylation at birth and mid-childhood, measured via the Infinium 450K array. METHODS/RESULTS Participants were from Project Viva, a pre-birth cohort of pregnant women and their children in Eastern Massachusetts. After exclusion of participants with maternal type 1 or 2 diabetes and gestational age <34 weeks, we used DNA methylation assays from 476 venous umbilical cord blood samples and a subset of 235 who additionally had peripheral blood samples available in mid-childhood (age 7-10 years). Among 392,918 CpG sites analyzed, birth weight-for-gestational age z-score was associated with cord blood DNA methylation at 34 CpGs (false discovery rate P < 0.05), after adjusting for maternal age, race/ethnicity, education, smoking, parity, delivery mode, pre-pregnancy BMI, gestational diabetes status, child sex, and estimated cord blood cell proportions based on a cord blood reference panel. Two of these CpGs were previously reported in epigenome-wide analyses of birth weight, and several other CpGs map to genes relevant to fetal growth and development. Namely, higher birth weight-for-gestational age was associated with higher methylation at four CpGs at the PBX1 locus (e.g., β (95% CI) for lead signal at cg06750897 = 1.9 (1.2, 2.6)), which encodes a transcription factor that regulates embryonic development. Birth weight-for-gestational age was also associated with mid-childhood blood DNA methylation at four of the 34 CpGs identified in cord blood analyses, including sites at the PBX1 locus described. CONCLUSIONS We identified CpG sites where birth weight-for-gestational age was associated with DNA methylation at birth, and for a subset of these sites, birth weight-for-gestational age was also associated with DNA methylation at mid-childhood.