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Genetic analysis of children with congenital ocular anomalies in three ecological regions of Nepal: a phase II of Nepal pediatric ocular diseases study.

ABSTRACT: BACKGROUND:Genetic eye diseases constitute a large and heterogeneous group of childhood ocular morbidity. Individual diseases may cause multiple structural anomalies and developmental features. Nepal Pediatric Ocular Disease Study (NPODS) was a population-based epidemiological study conducted across three ecological regions of Nepal to determine the prevalence and etiology of childhood ocular morbidity and blindness. In Phase II of this study, genetic analysis was performed for children who were found to have congenital ocular anomalies. METHOD:It was a cross sectional descriptive study. A total of 10,270 children across three different ecological regions in Nepal (Low lands, hills, and mountains) underwent ocular examinations in NPODS. Out of 374 (3.6%) of children with ocular abnormalities, 30 were thought to be congenital in nature. Targeted genetic analysis, including genotyping for genes specific to presenting phenotype, was performed for 25 children using serum samples. RESULTS:Out of 25 children, 18 had meaningful genetic results. Analysis revealed one missense alteration G12411T of Zinc Finger Homeobox 4 (ZFHX4) gene in one participant among 10 with congenital ptosis and another missense variation T?>?C P. Y374 C of Signaling Receptor and Transporter Retinol 6 (STRA6) gene in one participant among 3 with microphthalmos. CONCLUSION:The study is first of its kind from Nepal and mutant genes were unique to Nepalese Population. Further analysis of genetic factors is crucial to better understand genetic association with ocular diseases and conditions. This helps further in genetic counseling and probably gene therapy to prevent blindness from these conditions.

SUBMITTER: Adhikari S

PROVIDER: S-EPMC7510079 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Genetic analysis of children with congenital ocular anomalies in three ecological regions of Nepal: a phase II of Nepal pediatric ocular diseases study.

Adhikari Srijana S Thakur Neelam N Shrestha Ujjowala U Shrestha Mohan K MK Manshrestha Murarai M Thapa Bijay B Poudel Manish M Kunwar Ajaya A

BMC medical genetics 20200922 1

<h4>Background</h4>Genetic eye diseases constitute a large and heterogeneous group of childhood ocular morbidity. Individual diseases may cause multiple structural anomalies and developmental features. Nepal Pediatric Ocular Disease Study (NPODS) was a population-based epidemiological study conducted across three ecological regions of Nepal to determine the prevalence and etiology of childhood ocular morbidity and blindness. In Phase II of this study, genetic analysis was performed for children ...[more]

PMID: 32962661

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Project description:ObjectivesCannabis is a known teratogen. Data availability addressing both major congenital anomalies and cannabis use allowed us to explore their geospatial relationships.MethodsData for the years 1998 to 2009 from Canada Health and Statistics Canada was analyzed in R. Maps have been drawn and odds ratios, principal component analysis, correlation matrices, least squares regression and geospatial regression analyses have been conducted using the R packages base, dplyr, epiR, psych, ggplot2, colorplaner and the spml and spreml functions from package splm.ResultsMapping showed cannabis use was more common in the northern Territories of Canada in the Second National Survey of Cannabis Use 2018. Total congenital anomalies, all cardiovascular defects, orofacial clefts, Downs syndrome and gastroschisis were all found to be more common in these same regions and rose as a function of cannabis exposure. When Canada was dichotomized into high and low cannabis use zones by Provinces v Territories the Territories had a higher rate of total congenital anomalies 450.026 v 390.413 (O.R. = 1.16 95%C.I. 1.08-1.25, P = 0.000058; attributable fraction in exposed 13.25%, 95%C.I. 7.04-19.04%). In geospatial analysis in a spreml spatial error model cannabis was significant both alone as a main effect (P < 2.0 × 10) and in all its first and second order interactions with both tobacco and opioids from P < 2.0 × 10.ConclusionThese results show that the northern Territories of Canada share a higher rate of cannabis use together with elevated rates of total congenital anomalies, all cardiovascular defects, Down's syndrome and gastroschisis. This is the second report of a significant association between cannabis use and both total defects and all cardiovascular anomalies and the fourth published report of a link with Downs syndrome and thereby direct major genotoxicity. The correlative relationships described in this paper are confounded by many features of social disadvantage in Canada's northern territories. However, in the context of a similar broad spectrum of defects described both in animals and in epidemiological reports from Hawaii, Colorado, USA and Australia they are cause for particular concern and indicate further research.

Project description:BACKGROUND: Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain horse breed where it occurs at a high frequency among Silver colored horses. The Silver coat color is associated with mutations in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus. RESULTS: We performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype in PMEL17. Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color. CONCLUSION: The MCOA locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on UPP5, PMEL17ex11 and UPP6 strongly support the hypothesis that horses with the Cyst phenotype are heterozygous for the mutant allele and that horses with the MCOA phenotype are homozygous for the mutant allele.

Dataset Information

Genetic analysis of children with congenital ocular anomalies in three ecological regions of Nepal: a phase II of Nepal pediatric ocular diseases study.

Publications

Genetic analysis of children with congenital ocular anomalies in three ecological regions of Nepal: a phase II of Nepal pediatric ocular diseases study.

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