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Purpose: To describe the genetic and clinical spectrum of GUCY2D-associated retinopathies and to accurately establish their prevalence in a large cohort of patients., Design: Retrospective case series., Methods: Institutional study of 47 patients from 27 unrelated families with retinal dystrophies carrying disease-causing GUCY2D variants from the Fundación Jiménez Díaz hospital dataset of 8000 patients. Patients underwent ophthalmological examination and molecular testing by Sanger or exome sequencing approaches. Statistical and principal component analyses were performed to determine genotype-phenotype correlations., Results: Four clinically different associated phenotypes were identified: 66.7% of families with cone/cone-rod dystrophy, 22.2% with Leber congenital amaurosis, 7.4% with early-onset retinitis pigmentosa, and 3.7% with congenital night blindness. Twenty-three disease-causing GUCY2D variants were identified, including 6 novel variants. Biallelic variants accounted for 28% of patients, whereas most carried dominant alleles associated with cone/cone-rod dystrophy. The disease onset had statistically significant differences according to the functional variant effect. Patients carrying GUCY2D variants were projected into 3 subgroups by allelic combination, disease onset, and presence of nystagmus or night blindness. In contrast to patients with the most severe phenotype of Leber congenital amaurosis, 7 patients with biallelic GUCY2D had a later and milder rod form with night blindness in infancy as the first symptom., Conclusions: This study represents the largest GUCY2D cohort in which 4 distinctly different phenotypes were identified, including rare intermediate presentations of rod-dominated retinopathies. We established that GUCY2D is linked to about 1% of approximately 3000 molecularly characterized families of our cohort. All of these findings are critical for defining cohorts for inclusion in future clinical trials., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular (CV) risk factors are influenced by behavioral, cultural, and social factors, suggesting that acculturation plays a significant role in the emergency and growth of chronic disease. The objective of this study was to determine the relation between CV risk factors and the main components of acculturation, in Yaquis and Tepehuanos Indians from Mexico., Methods: This was a cross-sectional population-based study in Yaquis and Tepehuanos communities from the Yaqui Valley in Sonora and the Sierra Madre Occidental Mountains in Durango, in northwest Mexico. Acculturation status is different in both ethnic groups, with Tepehuanos living in small and remote communities retaining their traditional lifestyle and Yaquis living in well-communicated communities that have assumed Westernized lifestyles., Results: A total of 278 indigenous (120 Tepehuanos and 158 Yaquis) were randomly enrolled. Prevalence of obesity (48.1 and 6.7%, p <0.001), diabetes (18.3 and 0.83%, p <0.001), hypertriglyceridemia (43.0 and 15.0%, p <0.001), alcohol consumption (46.8 and 26.6%, p >0.001), and smoking (29.7 and 15.0%, p = 0.006) were significantly higher in Yaquis Indians. High blood pressure (6.3 and 3.3%, p = 0.40) and low HDL-cholesterol (42.4 and 34.2%, p = 0.22) were similar between Yaquis and Tepehuanos. Multivariate regression analysis adjusted by sex and age showed a significant association between calorie intake from saturated fat, but not other nutrients of customary diet, with hyperglycemia (OR 7.4, 95% CI 2.6-20.1), hypertriglyceridemia (OR 3.1, 95% CI 1.5-6.3), and obesity (OR 3.4, 95% CI 1.6-10.1)., Conclusions: Among the components of acculturation, intake of saturated fat is the most strongly associated with the development of CV risk factors.