Biomedical subjects

Atta Ur Rehman

Publications and source records attributed to Atta Ur Rehman.

3 recordsLinked to original sources

PubMed2026

Early-Onset Retinopathy in Patients With Variants in SLC6A6 Leading to Impaired Taurine Transport.

IMPORTANCE: Inherited retinal dystrophies are a group of disorders that may lead to progressive vision loss. Improved knowledge of their molecular genetics is important for accurate diagnosis or development of targeted therapies. OBJECTIVE: To identify pathogenic variants in the SLC6A6 gene (encoding TauT, the main transporter for taurine) and assess their role in the molecular pathogenesis of hereditary early-onset retinal dystrophy (EORD) in affected individuals from diverse ethnic backgrounds. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, multicenter observational study conducted between June 2019 and March 2025, involving 7 affected and 10 unaffected individuals from 4 unrelated families recruited in Pakistan, Italy, the US, and France. EXPOSURE: Pathogenic variants in SLC6A6 in individuals with EORD. MAIN OUTCOMES AND MEASURES: Genetic, clinical, and functional outcomes of pathogenic variants in SLC6A6 in individuals with Leber congenital amaurosis (LCA) and EORD. All patients underwent standard clinical examinations, including visual acuity, full-field electroretinography, and multimodal retinal imaging, followed by measurement of fasting plasma taurine levels. In vitro and ex vivo taurine transport and membrane trafficking assays in human embryonic kidney (HEK)-293 cells, as well as patient-derived fibroblasts, were also performed. RESULTS: All 7 affected individuals exhibited LCA/EORD, with extraocular findings in some. Genetic analysis identified homozygous pathogenic SLC6A6 variants in all affected individuals, while unaffected relatives were heterozygous carriers. Families 1 and 2 carried missense variants p.(Thr249Ile) and p.(Ala294Thr), while families 3 and 4 carried truncating variants-a deletion of exon 11 and p.(Thr113Ter), respectively. Functional studies demonstrated that both missense variants are associated with complete loss of taurine transport in HEK-293 cells and patient-derived fibroblasts. Additionally, irrespective of the variants considered, plasma taurine levels in affected individuals were reduced compared with heterozygous carriers (difference between means, -31.7 µmol/L; 95% CI, -42.7 to -20.8; P < .001) and healthy control individuals (difference between means, -37.7 µmol/L; 95% CI -41.6 to -33.8; P < .001). CONCLUSIONS AND RELEVANCE: These findings confirm and expand the role of biallelic variants in SLC6A6 in association with LCA/EORD due to impaired taurine transport. These findings suggest that patients with a diagnosis of SLC6A6-related LCA/EORD may be candidates for investigational oral taurine supplementation.

Humans↗

PubMed2025

BRCA1 Exon 11 Mutations in Breast Cancer: A Study From Pakistan.

Breast cancer ranks among the top causes of cancer-related deaths in women around the globe, with genetic mutations in the BRCA1 gene being a frequent cause of breast or ovarian cancer. This study investigates hotspot mutations in exon 11 of the BRCA1 gene among Pakistani women diagnosed with breast cancer. Thirty clinically diagnosed breast cancer patients, all women, were enrolled in the current study, and high-quality DNA was extracted from peripheral blood samples. Two of the twenty-five successfully sequenced samples had a homozygous missense variant (c.2312T > C: p.Leu771Ser) detected by Sanger sequencing after PCR amplification. Upon investigation in the ClinVar database, the identified variant showed conflicting interpretations of pathogenicity. Demographic data highlighted an early disease onset, showing that 56% of patients were under 50 years of age. The need for genetic screening was further supported by the fact that 24% of the patients had a positive family history of cancer. Our study emphasizes the necessity of screening BRCA1 gene mutations to better understand the pathogenic potential of the identified variants in the Pakistani population.

Humans↗

PubMed2025

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

BACKGROUND: Mutations in RP1 gene are the third leading cause of inherited retinal dystrophies (IRDs) in Pakistani families. PATIENTS: A two-generation consanguineous Pakistani family underwent both clinical and genetic analyses. Clinical examinations included visual acuity test, visual field, fundoscopy, and ocular coherence tomography (OCT). Whole exome sequencing (WES) was performed on the proband's DNA, and Sanger sequencing was performed to validate the WES findings. Splicing prediction tools such as Human Splicing Finder (HSF), NNSplice predictor, SpliceAI, MaxENTScan, and SpliceRover were used. RESULTS: A nuclear family of seven children, comprising five affected individuals (four males and one female) and two healthy siblings, was recruited from northwestern Pakistan. The proband was a 49-years old male who was presented with complaints of decreased visual acuity and night blindness since early childhood. Upon clinical evaluation, the proband appeared to have severely reduced visual acuity of hand movement (HM), bilateral visual field constriction, a waxy pale disc with vascular attenuation, pigmentary bone spicules at the periphery associated with chorioretinal degeneration, diffuse macular atrophy, and horizontal nystagmus in both of his eyes. Exome sequencing (ES) in the proband identified a homozygous splice site variant (NM_006269.2: c.615 + 1G > A) in RP1 gene. In-silico analysis, genotype-phenotype co-segregation study, and literature survey strongly supported the causality of the detected variant. CONCLUSIONS: We report a previously known pathogenic splice site variant of RP1 as the underlying cause of early-onset autosomal recessive retinitis pigmentosa (arRP) in a Pakistani family. We contemplate that the detected allele might constitute a mutational hotspot in RP1.

Humans↗