The current status of molecular diagnosis of inherited retinal dystrophies

Abstract

Currently, in approximately 50-60% of patients with nonsyndromic retinal dystrophy, the disease mechanism can be identified. The presence of pathogenic alleles in more than one gene is not uncommon. Retinal dystrophy, with relatively defined clinical presentations and a large but limited number of genes involved, is becoming a model for the next-generation study of molecular disease mechanisms.

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses

“…Genetic testing has the potential to accurately diagnose and predict disease occurrence in early and late-onset IRD Tajiguli et al, 2016;Weisschuh et al, 2016). Finding the genetic basis of IRDs is the first step of recruitment into gene mutation-based clinical trials (Wiggs and Pierce, 2013;Chiang and Trzupek, 2015;Lee and Garg, 2015;Nash et al, 2015). Sensitive and specific genetic tests are currently available at moderate cost for dozens of inherited eye diseases to genotype patients (Chiang and Trzupek, 2015;Consugar et al, 2015;Lee and Garg, 2015).…”

“…Finding the genetic basis of IRDs is the first step of recruitment into gene mutation-based clinical trials (Wiggs and Pierce, 2013;Chiang and Trzupek, 2015;Lee and Garg, 2015;Nash et al, 2015). Sensitive and specific genetic tests are currently available at moderate cost for dozens of inherited eye diseases to genotype patients (Chiang and Trzupek, 2015;Consugar et al, 2015;Lee and Garg, 2015). Compared with whole exome or genome sequencing with challenging data analysis, targeted genetic testing may improve cost efficiency and decrease turnaround time (Stone, 2003).…”

Sobre la terapia génica para enfermedades de la retina

“…No obstante, la calidad sin hipótesis conducida de este análisis a menudo conlleva una amplia cantidad de datos que resulta complicado interpretar. Por ejemplo, cada vez existen más pruebas de mutaciones múltiples en diferentes loci en pacientes con EHR, lo que desafía la concepción de que las EHR son defectos por un único gen [8] . Esto puede explicar en parte la heterogeneidad de su presentación fenotípica: pacientes con la misma mutación diagnosticada pueden tener defectos genéticos adicionales o modificadores polimorfos que explican las diferencias en la gravedad de la enfermedad o el índice de evolución de la enfermedad, por ejemplo.…”

Challenges confronting precision medicine in the context of inherited retinal disorders

“…Recently, the molecular diagnosis of IRD has been reviewed extensively. [6][7][8] Inherited retinal disorders provide a microcosm of the challenges that confront precision medicine. While most IRD are Mendelian disorders and relatively rare, collectively they constitute a major healthcare burden because of the longevity of individuals who are either born blind or progressively lose their vision in their teenage and young adult years.…”