A founder RDH5 splice site mutation leads to retinitis punctata albescens in two inbred Pakistani kindreds.
Conclusion: This is the first report of any pathogenic splice variant at first exon/intron boundary implicated in RPA and suggests another mechanism through which RDH5 variants could be associated with eye phenotype. This study also highlights the importance of a thorough phenotypic evaluation of heterozygous mutation carriers who may exhibit milder symptoms. PMID: 31933420 [PubMed - as supplied by publisher]
Bolz Herrmann Inherited retinal dystrophies (IRDs) are characterized by high clinical and genetic heterogeneity. A precise characterization is desirable for diagnosis and has impact on prognosis, patient counseling, and potential therapeutic options. Here, we demonstrate the effectiveness of the combination of in-depth retinal phenotyping and molecular genetic testing in complex pedigrees with different IRDs. Four affected Caucasians and two unaffected relatives were characterized including multimodal retinal imaging, functional testing, and targeted next-generation sequencing. A considerable intrafamilial phenotypi...
Conclusions: Patients presenting with PLAHF usually had retinal disorders. PMID: 31889465 [PubMed - as supplied by publisher]
Authors: Mechaussier S, Marlin S, Kaplan J, Rozet JM, Perrault I Abstract The specific association of Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (LCA-like) with sensorineural hearing loss (SHL) is uncommon. Recently, we ascribed some of these distinctive associations to dominant and de novo mutations in the β-tubulin 4B isotype-encoding gene (TUBB4B), providing a link between a sensorineural disease and anomalies in microtubules behavior. Here, we report 12 sporadic cases with LCA/SHL or LCA-like/SHL and no TUBB4B mutation. Trio-based whole exome sequencing (WES) identified diseas...
ConclusionsLow vision and nystagmus observed by parents, particularly in the first year of life, may represent a red flag, prompting an appropriate ophthalmological workup for inherited retinal dystrophy.
Conclusions: The mutations in C2orf71 reported in this study comprise protein truncation mutations, which are likely to be involved in the pathogenesis of this severe form of early onset CRD. PMID: 31819343 [PubMed - in process]
Conclusions: Our findings indicate that a recessive GNAT1 mutation found in this family could be the cause of the golden appearance of the fundus and negative ERGs with reduced a-waves, and nearly absent b-waves in the mixed rod-cone ERGs. PMID: 31696758 [PubMed - as supplied by publisher]
Authors: Ben M'Barek K, Habeler W, Regent F, Monville C Abstract In developed countries, blindness and visual impairment are caused mainly by diseases affecting the retina. These retinal degenerative diseases, including age-related macular dystrophy (AMD) and inherited retinal diseases such as retinitis pigmentosa (RP), are the predominant causes of human blindness worldwide and are responsible for more than 1.5 million cases in France and more than 30 million cases worldwide. Global prevalence and disease burden projections for next 20 years are alarming (Wong et al., Lancet Glob Health 2(2):e106-e116, 2014) and s...
Conclusions: Our data suggests that p.(F742C) in CACNA1F is an X-linked founder mutation in Ashkenazi Jews originating in Eastern Europe. This mutation causes a mild-to-moderate icCSNB phenotype, expressed in most female carriers. A targeted test for this variant in suspected patients may initiate diagnostic analysis. Our results highlight the relevance of WES in the clinic, allowing fast and accurate diagnosis for unclear and variable clinical phenotype and in pedigrees with multiple possible inheritance patterns. PMID: 31651202 [PubMed - as supplied by publisher]
Conclusion: Choroideremia is a disease with a significant unmet need. Interventions that can treat progression of the disease and improve visual and functional outcomes have the potential to reduce health care costs and enhance patient quality of life.
Conclusions: The patient's pedigree shows pseudodominant inheritance due to consanguineous parents. However, careful examination of the corneal findings strengthened the clinical suspicion of BCD, facilitating the molecular genetic confirmation of this autosomal recessive disease. PMID: 31638456 [PubMed - as supplied by publisher]