Clinical and genetic landscape of IRD in Portugal: pooled data from the nationwide IRD-PT registry

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 12, 2025

This study aims to characterize the clinical spectrum and genetic landscape of IRDs in Portugal. Multicentre, cross-sectional, cohort comprising consecutive patients with a diagnosis IRD available results, enroled IRD-PT registry (retina.com.pt). Among 1369 from 1125 families, most frequently observed phenotype was non-syndromic retinitis pigmentosa (40.8%). A genetically confirmed achieved 72.3% families. Consanguinity one-fifth cases, contributing higher frequency homozygous variants within this cohort. Disease-causing genotypes were distributed across 136 different genes, ABCA4 (13.0%), EYS (10.0%) USH2A (6.9%) being mutated genes. Overall, these results nationwide significantly advance our understanding Portugal, laying groundwork for future studies identify eligible targeted therapies describe natural history diseases.

Language: Английский

---

Deciphering the Genetic and Epidemiological Landscape of Inherited Retinal Diseases (IRDs) in a Cohort of Eastern Iranian Patients

Clinical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Inherited retinal diseases (IRDs) may have significant diagnostic challenges due to their genetic complexity and diverse inheritance patterns. Advanced genotyping tools like exome sequencing (ES) offer promising opportunities for identifying causative variants improving disease management. This retrospective study was aimed present prevalent pathogenic novel in patients diagnosed with IRDs using ES. We investigated 154 clinically IRDs, of which non-syndromic were more than syndromic form (~56% vs. ~44%). Out unrelated patients, 133 (~86%) genetically resolved, where retinitis pigmentosa the most common subtype (26% all resolved patients). Fifty-three previously known also 56 across IRD genes identified. Autosomal recessive predominated both forms (112/133, 84.21%), 46 variants. could be high rate consanguinity studied families (114/133 85.71%). The two reported ancestral founder TMEM67 (c.725A > G) BBS2 (c.471G A) genes, as well variant AIPL1 gene (c.834G A), our patients. Interestingly, identical compound heterozygote CEP290 (c.3167C A c.7024C T) identified cases. first attempt terms sample size diversity add current knowledge makeup a population from East Iran. Our findings can facilitate counselling classification especially challenging

Language: Английский

---

Pharmaceutical Waste Reduction in Hospitals: The Impact of Segregation Practices and Regulatory Compliance

Published: Jan. 1, 2025

Language: Английский

---

Exome sequencing identifies a homozygous splice site variant in RP1 as the underlying cause of autosomal recessive retinitis pigmentosa in a Pakistani family

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: March 3, 2025

Background Mutations in RP1 gene are the third leading cause of inherited retinal dystrophies (IRDs) Pakistani families.

Language: Английский

---

Deciphering the Genetic Basis of Degenerative and Developmental Eye Disorders in 50 Pakistani Consanguineous Families Using Whole-Exome Sequencing

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2715 - 2715

Published: March 18, 2025

Degenerative and developmental eye disorders, including inherited retinal dystrophies (IRDs), anophthalmia, congenital cataracts arise from genetic mutations, causing progressive vision loss or structural abnormalities. IRDs include a group of rare, genetically, clinically heterogeneous diseases. It is caused by variations in at least 324 genes, affecting numerous regions. In addition to IRDs, other disorders such as anophthalmia also have strong basis. Autosomal recessive are common consanguineous populations. many endogamous populations, those Pakistan, significant proportion IRD cases remain genetically undiagnosed. The present study investigated the genes 50 affected families. These unrelated families were recruited different provinces Pakistan Punjab, Khyber Pakhtoon Khwa, Sindh, Gilgit Baltistan, Azad Kashmir. Whole exome sequencing (WES) was conducted for proband each family. An in-house customized pipeline examined data, bioinformatics analysis predicted pathogenic effects identified variants. relevant DNA variants selected assessed parents healthy siblings via Sanger sequencing. WES 12 novel across 10 known IRD-associated genes. four most frequently implicated CRB1 (14.3%), GUCY2D (9.5%), AIPL1 CERKL (7.1%) that together accounted 40.4% all molecularly diagnosed cases. Additionally, 25 reported 19 cataracts-associated found. Among variants, p. Trp278X, stop–gain mutation (NM_014336) gene, causative variant detected. observed phenotype retinitis pigmentosa (46.5%) followed Leber amaurosis (18.6%). Furthermore, 98% pedigrees (49 out 50) autosomal cataracts. discovery likely atypical phenotypes, inter intra-familial variability underscores phenotypic heterogeneity degenerative Pakistani population further expands mutational spectrum associated with these ocular disorders.

Language: Английский

---

A comprehensive genetic landscape of inherited retinal diseases in a large Pakistani cohort

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: April 4, 2025

Language: Английский

---

A novel homozygous missense variant in POC1B causes cone dystrophy in a consanguineous Pakistani family

Ophthalmic Genetics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 9

Published: Nov. 20, 2024

Background Cone dystrophy is a heterogeneous hereditary retinal disorder with disease symptoms appearing in the late first or early second decades of life.

Language: Английский

---