Dataset Information

PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults.

ABSTRACT: Purpose:Genetic variation in PDE6C is associated with achromatopsia and cone dystrophy, with only a few reports of cone-rod dystrophy in the literature. We describe two pediatric and two adult patients with PDE6C related cone and cone-rod dystrophy and the first longitudinal data of a pediatric patient with PDE6C-related cone dystrophy. Methods:This cohort of four patients underwent comprehensive ophthalmologic evaluation at the National Eye Institute's Ophthalmic Genetics clinic, including visual field testing, retinal imaging and electroretinogram (ERG). Next-generation sequencing-based genetic testing was performed and subsequent analysis of the variants was done through three-dimensional protein models generated by Phyre2 and Chimera. Results:All cases shared decreased best-corrected visual acuity and poor color discrimination. Three of the four patients had a cone-rod dystrophy, presenting with an ERG showing decreased amplitude on both photopic and scotopic waveforms and a mild to moderately constricted visual field. One of the children was diagnosed with cone dystrophy, having a preserved peripheral field. The children had none to minor structural retinal changes, whereas the adults had clear macular dystrophy. Conclusions:PDE6C-related cone-rod dystrophy consists of a severe phenotype characterized by early-onset nystagmus, decreased best-corrected visual acuity, poor color discrimination, progressive constriction of the visual field, and night blindness. Our work contributes with valuable information toward understanding the visual prognosis and allelic heterogeneity of PDE6C-related cone and cone-rod dystrophy.

SUBMITTER: Daich Varela M

PROVIDER: S-EPMC7545085 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults.

Daich Varela Malena M Ullah Ehsan E Yousaf Sairah S Brooks Brian P BP Hufnagel Robert B RB Huryn Laryssa A LA

Investigative ophthalmology & visual science 20201001 12

<h4>Purpose</h4>Genetic variation in PDE6C is associated with achromatopsia and cone dystrophy, with only a few reports of cone-rod dystrophy in the literature. We describe two pediatric and two adult patients with PDE6C related cone and cone-rod dystrophy and the first longitudinal data of a pediatric patient with PDE6C-related cone dystrophy.<h4>Methods</h4>This cohort of four patients underwent comprehensive ophthalmologic evaluation at the National Eye Institute's Ophthalmic Genetics clinic, ...[more]

PMID: 33001157

Similar Datasets

Project description:Some sheep breeds are naturally prolific, and they are very informative for the studies of reproductive genetics and physiology. Major genes increasing litter size (LS) and ovulation rate (OR) were suspected in the French Grivette and the Polish Olkuska sheep populations, respectively. To identify genetic variants responsible for the highly prolific phenotype in these two breeds, genome-wide association studies (GWAS) followed by complementary genetic and functional analyses were performed. Highly prolific ewes (cases) and normal prolific ewes (controls) from each breed were genotyped using the Illumina OvineSNP50 Genotyping Beadchip. In both populations, an X chromosome region, close to the BMP15 gene, harbored clusters of markers with suggestive evidence of association at significance levels between 1E(-05) and 1E(-07). The BMP15 candidate gene was then sequenced, and two novel non-conservative mutations called FecX(Gr) and FecX(O) were identified in the Grivette and Olkuska breeds, respectively. The two mutations were associated with the highly prolific phenotype (p FecX (Gr) = 5.98E(-06) and p FecX(O) = 2.55E(-08)). Homozygous ewes for the mutated allele showed a significantly increased prolificacy (FecX(Gr)/FecX(Gr), LS = 2.50 ± 0.65 versus FecX(+)/FecX(Gr), LS = 1.93 ± 0.42, p<1E(-03) and FecX(O)/FecX(O), OR = 3.28 ± 0.85 versus FecX(+)/FecX(O), OR = 2.02 ± 0.47, p<1E(-03)). Both mutations are located in very well conserved motifs of the protein and altered the BMP15 signaling activity in vitro using a BMP-responsive luciferase test in COV434 granulosa cells. Thus, we have identified two novel mutations in the BMP15 gene associated with increased LS and OR. Notably, homozygous FecX(Gr)/FecX(Gr) Grivette and homozygous FecX(O)/FecX(O) Olkuska ewes are hyperprolific in striking contrast with the sterility exhibited by all other known homozygous BMP15 mutations. Our results bring new insights into the key role played by the BMP15 protein in ovarian function and could contribute to a better understanding of the pathogenesis of women's fertility disorders.

Project description:ImportanceUp to 50% of patients may have hidradenitis suppurativa (HS) onset between age 10 and 21 years. To our knowledge, little is known about how adolescents with HS utilize health care during their journey to receiving a diagnosis.ObjectiveTo assess the clinical characteristics and health care utilization patterns of pediatric vs adult patients with HS.Design, setting, and participantsThis retrospective cohort study included adult and pediatric patients with HS claims from the MarketScan medical claims database during the study period, January 1, 2012, to December 31, 2016. The data were analyzed between March 1 and March 31, 2021.ExposuresClinical characteristics and health care utilization patterns of pediatric vs adult patients with HS.Main outcomes and measuresHealth care utilization patterns were examined and included concurrent diagnoses, outpatient care by discipline, and emergency/urgent care and inpatient claims.ResultsThis study included 8727 members, comprising 1094 pediatric (155 male [14.2%] and 939 female patients [85.8%]; mean [SD] age, 14.3 [2.47] years) and 7633 adult patients (1748 men [22.9%] and 5885 women [77.1%]; mean [SD] age, 37.2 [12.99] years). Pediatric patients were likely to see pediatricians, dermatologists, emergency department (ED) staff, and family physicians before diagnosis and commonly received diagnoses of folliculitis and comedones. Pediatric patients with HS had high rates of comorbid skin and general medical conditions, including acne vulgaris (558 [51.0%]), acne conglobata (503 [45.9%]), obesity (369 [33.7%]), and anxiety disorders (367 [33.6%]). A higher percentage of pediatric than adult patients had HS-specific claims for services rendered by emergency and urgent care physicians (35.6% vs 28.2%; P < .001; and 18.1% vs 13.4%; P < .001; respectively). However, adult patients were more likely to have inpatient stays (2.38% vs 4.22%; P = .002). Pediatric patients had 2.24 ED claims per person, while adults had 3.5 claims per person. The mean cost per ED claim was similar between groups ($413.27 vs $682.54; P = .18). The largest component of the total 5-year disease-specific cost was the cost of inpatient visits for pediatric and adult patients with HS.Conclusions and relevanceThis cohort study suggests that pediatric patients utilize high-cost ED care when HS can often be treated as an outpatient. These data suggest that there are opportunities to improve recognition of HS in pediatric patients by nondermatologists and dermatologists.

Dataset Information

PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults.

Publications

PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets