Frontotemporal degeneration (FTD) is an umbrella term encompassing a range of rare neurodegenerative disorders that cause progressive declines in cognition, behavior, and personality. Hearing directly from individuals living with FTD and their care partners is critical in optimizing care, identifying meaningful clinical trial endpoints, and improving research recruitment and retention. The current paper presents a subset of data from the FTD Insights Survey, chronicling the diagnostic journey, symptoms, and the impact of FTD on distress, quality of life, and independence, in the mild to moderate stages of the disease.
View Article and Find Full Text PDFBackground: The internet has become an increasingly popular medium for parents to obtain health information. More studies investigating the impact of paid digital marketing campaigns for parents on promoting children's healthy development are needed.
Objective: This study aims to explore the outcomes of a paid digital marketing campaign, which occurred from 2018 to 2020, to promote messages about parent-engaged developmental monitoring and ultimately direct parents to the Centers for Disease Control and Prevention's (CDC's) Milestone Tracker app, a mobile health (mHealth) app developed by the CDC.
Purpose: X-linked retinitis pigmentosa can manifest in female carriers with widely variable severity, whereas others remain unaffected. The contribution of X-chromosome inactivation (XCI) to phenotypic variation has been postulated but not demonstrated. Furthermore, the impact of genotype and genetic modifiers has been demonstrated in affected males but has not been well established in female carriers.
View Article and Find Full Text PDFGenetic testing of probands in families with an initial diagnosis of autosomal dominant retinitis pigmentosa (adRP) usually confirms the diagnosis, but there are exceptions. We report results of genetic testing in a large cohort of adRP families with an emphasis on exceptional cases including X-linked RP with affected females; homozygous affected individuals in families with heterozygous, dominant disease; and independently segregating mutations in the same family. Genetic testing was conducted in more than 700 families with a provisional or probable diagnosis of adRP.
View Article and Find Full Text PDFThe cyclic nucleotide-gated (CNG) channel - composed of CNGA3 and CNGB3 subunits - mediates the influx of cations in cone photoreceptors after light stimulation and thus is a key element in cone phototransduction. Mutations in CNGA3 and CNGB3 are associated with achromatopsia, a rare autosomal recessive retinal disorder. Here, we demonstrate that the presence of an early nonsense mutation in CNGA3 induces the usage of a downstream alternative translation initiation site giving rise to a short CNGA3 isoform.
View Article and Find Full Text PDFPurpose: With recent availability of next-generation sequencing (NGS), it is becoming more common to pursue disease-targeted panel testing rather than traditional sequential gene-by-gene dideoxy sequencing. In this report, we describe using NGS to identify multiple disease-causing mutations that contribute concurrently or independently to retinal dystrophy in three relatively small families.
Methods: Family members underwent comprehensive visual function evaluations, and genetic counseling including a detailed family history.
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.
Mol Genet Metab Rep
December 2016
Peroxisomal biogenesis disorders (PBD) are caused by mutations in genes, and are typically diagnosed with biochemical testing in plasma followed by confirmatory testing. Here we report the unusual diagnostic path of a child homozygous for PEX1 p.G843D.
View Article and Find Full Text PDFPurpose: To identify the underlying cause of disease in a large family with North Carolina macular dystrophy (NCMD).
Methods: A large four-generation family (RFS355) with an autosomal dominant form of NCMD was ascertained. Family members underwent comprehensive visual function evaluations.
Whole-genome linkage mapping identified a region on chromosome 10q21.3-q22.1 with a maximum LOD score of 3.
View Article and Find Full Text PDFPurpose: To determine whether annual decline in visual field sensitivity is greater in the transition zone at the edge of the frequency-domain optical coherence tomography (fdOCT) inner segment ellipsoid zone (EZ) than at other locations in the visual field.
Design: Prospective, longitudinal, observational study.
Participants: Forty-four patients with X-linked retinitis pigmentosa (XLRP) resulting from a mutation in the RPGR gene.
Invest Ophthalmol Vis Sci
September 2014
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.
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.
Retinitis pigmentosa (RP) is a devastating form of retinal degeneration, with significant social and professional consequences. Molecular genetic information is invaluable for an accurate clinical diagnosis of RP due to its high genetic and clinical heterogeneity. Using a gene capture panel that covers 163 of the currently known retinal disease genes, including 48 RP genes, we performed a comprehensive molecular screening in a collection of 123 RP unsettled probands from a wide variety of ethnic backgrounds, including 113 unrelated simplex and 10 autosomal recessive RP (arRP) cases.
View Article and Find Full Text PDFBackground: Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP) are inherited retinal diseases that cause early onset severe visual impairment. An accurate molecular diagnosis can refine the clinical diagnosis and allow gene specific treatments.
Methods: We developed a capture panel that enriches the exonic DNA of 163 known retinal disease genes.
Purpose: We determined the fraction of families in a well-characterized cohort with a provisional diagnosis of autosomal dominant retinitis pigmentosa (adRP) that have disease-causing mutations in the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene or the retinitis pigmentosa 2 (RP2) gene.
Methods: Families with a provisional clinical diagnosis of adRP, and a pedigree consistent with adRP but no male-to-male transmission were selected from a cohort of 258 families, and tested for mutations in the RPGR and RP2 genes with di-deoxy sequencing. To facilitate testing of RPGR in "adRP" families that had no male members available for testing, the repetitive and purine-rich ORF15 of RPGR was subcloned and sequenced in heterozygous female subjects from 16 unrelated families.
Invest Ophthalmol Vis Sci
December 2012
Purpose: To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2.
Methods: Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity.
Objective: To confirm altered perfusion within tibial bone marrow lesions (BMLs) and improve our understanding on the relationship between BMLs and pain in knee osteoarthritis (OA).
Methods: Participants with moderate to severe knee OA were recruited and pain was assessed using the pain subscale of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Subchondral tibial BMLs were identified and graded on magnetic resonance imaging (MRI) proton density-weighted (PDW) fat suppressed images.
Leber congenital amaurosis (LCA) is an autosomal recessive retinal dystrophy that manifests with genetic heterogeneity. We sequenced the exome of an individual with LCA and identified nonsense (c.507G>A, p.
View Article and Find Full Text PDFBackground: 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.
Mutations in RPGR account for over 70% of X-linked retinitis pigmentosa (XlRP), characterized by retinal degeneration and eventual blindness. The clinical consequences of RPGR mutations are highly varied, even among individuals with the same mutation: males demonstrate a wide range of clinical severity, and female carriers may or may not be affected. This study describes the phenotypic diversity in a cohort of 98 affected males from 56 families with RPGR mutations, and demonstrates the contribution of genetic factors (i.
View Article and Find Full Text PDFBackground: 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.
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.
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