A nonsense mutation in C8orf37 linked with retinitis pigmentosa, early macular degeneration, cataract, and myopia in an arRP family from North India.

OBJECTIVE: This study aimed at identifying the underlying genetic defect in a consanguineous autosomal recessive retinitis pigmentosa (arRP) (RP-1175) family having RP with early macular degeneration, cataract, and myopia. METHODS: Whole-exome sequencing (WES) was performed on the DNA of the proband, and variants observed were validated in the rest of the affected and unaffected family members by Sanger sequencing. Different bioinformatics tools were applied to access the pathogenicity of the observed variant. RESULTS: A nonsense mutation i.e., c.555G > A (p.Trp185Ter) in C8orf37 in homozygous form, has been identified that segregated with the disease in the affected members. c.555G > A was absent in unaffected family members and in 107 ethnically matched controls, therefore ruling out its possibility of being a polymorphism. CONCLUSIONS: Present study identifies a nonsense mutation (c.555G > A) at codon 185 in C8orf37 linked with arRP, early macular degeneration, posterior subcapsular cataract, and myopia. The identical mutation has previously been reported in a Pakistani family with isolated RP and in a Chinese family with RP and macular degeneration. This variable expressivity of the identified mutation c.555G > A in C8orf37 in the analyzed Indian family may be attributed to the presence of the modifier alleles. Also, Trp185 might be a mutation hotspot in Asian arRP patients and in the future, p.Trp185Ter in C8orf37 may be tested during initial screening in arRP cases especially belonging to a similar population.

Alcohol consumption and 5-year change in left atrial volume among patients with coronary heart disease: results from the Heart and Soul study.

BACKGROUND: Heavy alcohol consumption is a risk factor for developing atrial fibrillation, but whether chronic alcohol use affects left atrial volume is unknown. We evaluated the association of self-reported alcohol consumption with 5-year change in left atrial volume among patients with coronary heart disease (CHD). METHODS: We studied 601 participants with stable CHD who underwent 2-dimensional echocardiography at baseline (2000-2002) and after 5 years of follow-up (2005-2007). Alcohol consumption was determined at baseline with the use of the Alcohol Use Disorders Identification Test consumption questions (AUDIT-C), with a standard cutoff point of ≥3 used to define at-risk drinking. We used logistic regression to evaluate the association of baseline alcohol use with 5-year increase in left atrial end-systolic volume index (defined as being in the highest tertile of percent change). RESULTS: After adjustment for covariates, each standard deviation (2.4-point) increase in AUDIT-C score was associated with a 24% greater odds of experiencing a 5-year increase in left atrial volume index (adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 1.04-1.48; P = .02). Compared with the 369 participants who had AUDIT-C scores of <3, the 171 participants with scores of 3-5 had a 51% greater odds (OR 1.51, 95% CI, 1.11-2.25) and the 61 participants with scores of >5 a 98% greater odds (OR 1.98, 95% CI, 1.10-3.56) of experiencing a 5-year increase in left atrial volume index. CONCLUSIONS: In patients with CHD, heavier alcohol consumption is associated with a 5-year increase in left atrial volume. Whether greater left atrial volume contributes to the increased risk of atrial fibrillation associated with alcohol use deserves further study.