Identification of RP1 as the genetic cause of retinitis pigmentosa in a multi-generational pedigree using Extremely Low-Coverage Whole Genome Sequencing (XLC-WGS).

MOTIVATION: Next-generation sequencing (NGS) technologies are decisive for discovering disease-causing variants, although their cost limits their utility in a clinical setting. A cost-mitigating alternative is an extremely low coverage whole-genome sequencing (XLC-WGS). We investigated its use to identify causal variants within a multi-generational pedigree of individuals with retinitis pigmentosa (RP). Causing progressive vision loss, RP is a group of genetically heterogeneous eye disorders with approximately 60 known causal genes. RESULTS: We performed XLC-WGS in seventeen members of this pedigree, including three individuals with a confirmed diagnosis of RP. Sequencing data were processed using Illumina's DRAGEN pipeline and filtered using Illumina's genotype quality score metric (GQX). The resulting variants were analyzed using Expert Variant Interpreter (eVai) from enGenome as a prioritization tool. A nonsense known mutation (c.1625C > G; p.Ser542*) in exon 4 of the RP1 gene emerged as the most likely causal variant. We identified two homozygous carriers of this variant among the three sequenced RP cases and three heterozygous individuals with sufficient coverage of the RP1 locus. Our data show the utility of combining pedigree information with XLC-WGS as a cost-effective approach to identify disease-causing variants.

National survey of blindness and visual impairment in Guatemala, 2015 / Pesquisa nacional sobre cegueira e deficiência visual na Guatemala, 2015

ABSTRACT - Purpose: To estimate the prevalence of blindness and visual impairment in older adults living in Guatemala. Methods: Participants ³50 years of age were selected using random cluster sampling and evaluated using the Rapid Assessment of Avoidable Blindness method. Visual acuity was measured, and the lens was examined. If presenting visual acuity was <20/60, it was also tested with a pinhole and fundoscopy was performed. Blindness and visual impairment were classified as moderate visual impairment (presenting visual acuity <20/60 to 20/200), severe visual impairment (presenting visual acuity <20/200 to 20/400), or blindness (presenting visual acuity <20/400). The primary cause of blindness or visual impairment in each eye was determined, and if the cause was cataracts, the barriers to treatment were assessed. Results: The study included 3,850 people ³50 years of age, of whom 3,760 (97.7%) were examined. The age- and sex-adjusted prevalence of blindness was 2.9% (95% confidence interval, 2.0%-3.8%), while 5.2% (4.0%-6.4%) presented with severe visual impairment, and 27.6% (23.3%-32.0%) presented with moderate visual impairment. Cataracts were the leading cause of blindness (77.6%), followed by other posterior segment diseases (6.0%). Cataracts caused 79.4% of cases of severe visual impairment, while uncorrected refractive errors caused 67.9% of cases of moderate visual impairment. Following cataract surgery, 75% of participants had a presenting visual acuity of 20/200 or better, and in 19.0% of participants, visual acuity was not better than 20/200 with correction. Cost was the main barrier to cataract surgery (56.7%). Conclusions: The prevalence of blindness in older adults is higher in Guatemala than in most Central American countries. Most cases of blindness and visual impairment were either preventable or treatable. Increased availability of affordable, high-quality cataract treatment would have a substantial impact on blindness prevention.

RESUMO - Objetivo: Estimar a prevalência de cegueira e de­fi­ciência visual em idosos que vivem na Guatemala. Métodos: Indivíduos com idade ³50 anos foram selecionados por amos­tragem aleatória por conglomerados, e os participantes do estudo foram avaliados pelo método de Avaliação Rápida da Cegueira Evitável. A acuidade visual foi medida e o cristalino foi examinado. Se a acuidade visual apresentada fosse <20/60, então também foi testada com um buraco estenopeico e a fundoscopia realizada. A cegueira e a deficiência visual foram classificadas como deficiência visual moderada com acuidade visual <20/60-20/200; deficiência visual grave com acuidade visual <20/200-20/400; ou cegueira com acuidade visual <20/400. A principal causa de cegueira ou deficiência visual em cada olho foi determinada, e naqueles com catarata, as barreiras ao tratamento foram avaliadas. Resultados: O estudo incluiu 3.850 pessoas com ³50 anos de idade; 3.760 (97,7%) foram examinadas. A prevalência de cegueira ajustada à idade e ao sexo foi de 2,9% (intervalo de confiança de 95%, 2,0-3,8%), 5,2% (4,0-6,4%) deficiência visual grave e 27,6% (23,3-32,0%) deficiência visual moderada. A catarata foi a principal de cegueira (77,6%), seguida de outras doenças do segmento posterior (6,0%). Catarata causada por 79,4% de deficiência visual grave, enquanto erros refrativos não corrigidos causaram 67,9% de deficiência visual moderada. Após a cirurgia de catarata, 75% dos participantes tiveram uma acuidade de 20/200, ou melhor, e 19,0% a deficiência visual não foi melhor do que 20/200 com a correção. O custo foi a principal barreira à cirurgia de catarata (56.7%). Conclusões: A prevalência de cegueira em idosos é maior na Guatemala do que na maioria dos outros países da América Central. A maioria dos casos de cegueira e deficiência visual era evitável ou tratável. O aumento da disponibilidade de tratamento de catarata a preços acessíveis e de alta qualidade teria um impacto substancial na prevenção da cegueira.

National survey of blindness and visual impairment in Guatemala, 2015.

PURPOSE: To estimate the prevalence of blindness and visual impairment in older adults living in Guatemala. METHODS: Participants ³50 years of age were selected using random cluster sampling and evaluated using the Rapid Assessment of Avoidable Blindness method. Visual acuity was measured, and the lens was examined. If presenting visual acuity was <20/60, it was also tested with a pinhole and fundoscopy was performed. Blindness and visual impairment were classified as moderate visual impairment (presenting visual acuity <20/60 to 20/200), severe visual impairment (presenting visual acuity <20/200 to 20/400), or blindness (presenting visual acuity <20/400). The primary cause of blindness or visual impairment in each eye was determined, and if the cause was cataracts, the barriers to treatment were assessed. RESULTS: The study included 3,850 people ³50 years of age, of whom 3,760 (97.7%) were examined. The age- and sex-adjusted prevalence of blindness was 2.9% (95% confidence interval, 2.0%-3.8%), while 5.2% (4.0%-6.4%) presented with severe visual impairment, and 27.6% (23.3%-32.0%) presented with moderate visual impairment. Cataracts were the leading cause of blindness (77.6%), followed by other posterior segment diseases (6.0%). Cataracts caused 79.4% of cases of severe visual impairment, while uncorrected refractive errors caused 67.9% of cases of moderate visual impairment. Following cataract surgery, 75% of participants had a presenting visual acuity of 20/200 or better, and in 19.0% of participants, visual acuity was not better than 20/200 with correction. Cost was the main barrier to cataract surgery (56.7%). CONCLUSIONS: The prevalence of blindness in older adults is higher in Guatemala than in most Central American countries. Most cases of blindness and visual impairment were either preventable or treatable. Increased availability of affordable, high-quality cataract treatment would have a substantial impact on blindness prevention.