A Novel Dominant Mutation in SAG, the Arrestin-1 Gene, Is a Common Cause of Retinitis Pigmentosa in Hispanic Families in the Southwestern United States.

Purpose: To identify the causes of autosomal dominant retinitis pigmentosa (adRP) in a cohort of families without mutations in known adRP genes and consequently to characterize a novel dominant-acting missense mutation in SAG.

Methods: Patients underwent ophthalmologic testing and were screened for mutations using targeted-capture and whole-exome next-generation sequencing. Confirmation and additional screening were done by Sanger sequencing.

A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa.

Purpose: To identify the cause of retinitis pigmentosa (RP) in UTAD003, a large, six-generation Louisiana family with autosomal dominant retinitis pigmentosa (adRP).

Methods: A series of strategies, including candidate gene screening, linkage exclusion, genome-wide linkage mapping, and whole-exome next-generation sequencing, was used to identify a mutation in a novel disease gene on chromosome 10q22.1.

Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa.

Purpose: The purpose of this project was to determine the spectrum and frequency of mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) that cause autosomal dominant retinitis pigmentosa (adRP).

Methods: A well-characterized adRP cohort of 251 families was tested for mutations in the exons and intron/exon junctions of SNRNP200 using fluorescent dideoxy sequencing. An additional 21 adRP families from the eyeGENE® Network were tested for possible mutations.

A randomized trial of DHA intake during infancy: school readiness and receptive vocabulary at 2-3.5 years of age.

Background: Studies investigating the effects of docosahexaenoic acid (DHA) in infant formula on language development yield conflicting results. No study to date has investigated the effects of DHA in infant formula on school readiness.

Aim: To determine the effects of different dietary concentrations of DHA provided during the first 12 months of life on language development and school readiness.

Cognitive function in 18-month-old term infants of the DIAMOND study: a randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid.

Background: Studies investigating cognitive outcomes following docosahexaenoic acid (DHA) supplementation of infant formula yield conflicting results, perhaps due to inadequate dietary concentrations.

Aim: To determine the optimal DHA concentration in term formula to support cognitive maturation.

Design: This was a double-masked, randomized, controlled, prospective trial.

Identification of disease-causing mutations in autosomal dominant retinitis pigmentosa (adRP) using next-generation DNA sequencing.

Purpose: To determine whether massively parallel next-generation DNA sequencing offers rapid and efficient detection of disease-causing mutations in patients with monogenic inherited diseases. Retinitis pigmentosa (RP) is a challenging application for this technology because it is a monogenic disease in individuals and families but is highly heterogeneous in patient populations. RP has multiple patterns of inheritance, with mutations in many genes for each inheritance pattern and numerous, distinct, disease-causing mutations at each locus; further, many RP genes have not been identified yet.

Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo.

Background: Several studies found a benefit of long-chain polyunsaturated fatty acid (LCP) supplementation for visual or mental development, but others found no benefit. Likely contributors to differences among studies are the amount of LCP supplementation, functional outcomes, and sample size.

Objective: We evaluated LCP supplementation in amounts typical for human milk (based on local and worldwide surveys) in a large cohort of infants by using sweep visual evoked potential (VEP) acuity as the functional outcome.

Duration of long-chain polyunsaturated fatty acids availability in the diet and visual acuity.

Background: Little is known about the critical period during which the dietary supply of long-chain polyunsaturated fatty acids (LCPUFAs) may influence the maturation of visual cortical function in term infants.

Aim: To define the relationship between duration of dietary LCPUFA supply and visual acuity at 52 weeks of age.

Study Design: Data from 243 infants who participated in four randomized clinical trials of LCPUFA supplementation of infant formula at a single research center were combined.

Risk factors for accommodative esotropia among hypermetropic children.

Purpose: Identification of risk factors for accommodative esotropia may help to determine which children with hyperopia may benefit from early spectacle correction or preventive therapy.

Methods: Participants in the family history study were 95 consecutive patients, aged 18 to 60 months, with accommodative esotropia. Participants in the binocular sensory function study were a subgroup of 41 children enrolled in the family history study within 1 month of onset, while the esodeviation was still intermittent.

Maturation of visual acuity is accelerated in breast-fed term infants fed baby food containing DHA-enriched egg yolk.

Between 6 and 12 mo of age, blood levels of the (n-3) long-chain PUFA, docosahexaenoic acid (DHA), in breast-fed infants typically decrease due to diminished maternal DHA stores and the introduction of DHA-poor solid foods displacing human milk as the primary source of nutrition. Thus, we utilized a randomized, clinical trial format to evaluate the effect of supplemental DHA in solid foods on visual development of breast-fed infants with the primary outcome, sweep visual-evoked potential (VEP) acuity, as an index for maturation of the retina and visual cortex. At 6 mo of age, breast-fed infants were randomly assigned to receive 1 jar (113 g)/d of baby food containing egg yolk enriched with DHA (115 mg DHA/100 g food; n = 25) or control baby food (0 mg DHA; n = 26).

A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa.

Purpose: Low docosahexaenoic acid (DHA) in X-linked retinitis pigmentosa (XLRP) may influence retinal function. The goals of this study were to elevate blood DHA levels and determine the effect on the rate of disease progression.

Design: In a 4-year prospective randomized clinical trial, male patients with XLRP (mean age = 16 years; range = 4-38 years) received DHA (400 mg/d; n = 23; +DHA group) or placebo (n = 21) capsules.

Biological safety assessment of docosahexaenoic acid supplementation in a randomized clinical trial for X-linked retinitis pigmentosa.

Background: In a 4-year placebo-controlled trial to elevate blood docosahexaenoic acid levels in patients with X-linked retinitis pigmentosa (XLRP), the goal was to assess the potential benefit of docosahexaenoic acid supplementation in altering disease progression. However, docosahexaenoic acid (22:6omega3) is a highly unsaturated fatty acid and considered a target molecule for free-radical oxidative damage. Thus, nutritional provision of docosahexaenoic acid might lead to an increase in antioxidant stress.

Visual function in breast-fed term infants weaned to formula with or without long-chain polyunsaturates at 4 to 6 months: a randomized clinical trial.

Objective: Breast-fed infants receive docosahexaenoic acid (DHA) and arachidonic acid (ARA) in their diet. Upon weaning, infants lose this dietary source of long-chain polyunsaturates because many commercial formulas do not contain these important constituents for neural membrane biogenesis. We evaluated the benefits of postweaning dietary supplementation of DHA + ARA on visual maturation.