scholarly journals Inherited Retinal Diseases Due to RPE65 Variants: From Genetic Diagnostic Management to Therapy

2021 ◽  
Vol 22 (13) ◽  
pp. 7207
Author(s):  
Manar Aoun ◽  
Ilaria Passerini ◽  
Pietro Chiurazzi ◽  
Marianthi Karali ◽  
Irene De Rienzo ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Patient Management ◽  
Autosomal Recessive ◽  
Age Of Onset ◽  
Retinal Dystrophy ◽  
Multidisciplinary Teams ◽  
Retinal Diseases ◽  
Diagnostic Management ◽  
Generation Sequencing

Inherited retinal diseases (IRDs) are a heterogeneous group of conditions that include retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EO[S]RD), which differ in severity and age of onset. IRDs are caused by mutations in >250 genes. Variants in the RPE65 gene account for 0.6–6% of RP and 3–16% of LCA/EORD cases. Voretigene neparvovec is a gene therapy approved for the treatment of patients with an autosomal recessive retinal dystrophy due to confirmed biallelic RPE65 variants (RPE65-IRDs). Therefore, the accurate molecular diagnosis of RPE65-IRDs is crucial to identify ‘actionable’ genotypes—i.e., genotypes that may benefit from the treatment—and is an integral part of patient management. To date, hundreds of RPE65 variants have been identified, some of which are classified as pathogenic or likely pathogenic, while the significance of others is yet to be established. In this review, we provide an overview of the genetic diagnostic workup needed to select patients that could be eligible for voretigene neparvovec treatment. Careful clinical characterization of patients by multidisciplinary teams of experts, combined with the availability of next-generation sequencing approaches, can accelerate patients’ access to available therapeutic options.

scholarly journals New Compound Heterozygous CYP4V2 Mutations in Bietti Crystalline Corneoretinal Dystrophy

2020 ◽  
Author(s):  
Ting Wang ◽  
Qingshan Chen ◽  
Longhao Kuang ◽  
Jiantao Wang ◽  
Xiaohe Yan
Keyword(s):  
Autosomal Recessive ◽  
Frameshift Mutation ◽  
Retinal Dystrophy ◽  
Genetic Diagnosis ◽  
Compound Heterozygous ◽  
Retinal Diseases ◽  
Sequence Capture ◽  
Pathogenic Genes ◽  
Compound Heterozygous Mutations ◽  
Targeted Sequence Capture

Abstract Background: Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal dystrophy which is caused by the mutations of CYP4V2.Here we identified new CYP4V2compound heterozygous mutations in BCD.Methods:381 pathogenic genes related to retinal diseases were screened by targeted sequence capture array techniques and confirmed by Sanger sequencing.Results:Two female siblings with BCD carry two compound heterozygous mutations in CYP4V2. One was missense mutation c.1198C>T (p.R400C) and the other was frameshift mutation c.802-8_810delinsGC (p.V268_E329del).Optical coherence tomography (OCT) showed that the ellipsoid zone was absent in the macular regions and electroretinogram (ERG) revealed poor cone and rod responses. Conclusions:Newcompound heterozygous mutations in CYP4V2 are related to the BCD.Our study expands our knowledge of heterogenic phenotypes and genotypes through genetic diagnosis of the BCD patients.

“ There is No Cure for Stargardt’s”: The Prognosis and Rehabilitation of a Patient with Genetically Confirmed Abca 4 Mutations

2020 ◽  
pp. 237-242
Keyword(s):  
Gene Therapy ◽  
Genetic Counseling ◽  
Case Report ◽  
Autosomal Recessive ◽  
Retinal Dystrophy ◽  
Macular Dystrophy ◽  
African American Female ◽  
Abca4 Gene ◽  
Inherited Retinal Dystrophy ◽  
Comprehensive Rehabilitation

Background: Stargardt’s macular dystrophy is an autosomal recessive inherited retinal dystrophy associated with mutation in the ABCA4 gene. Although there are no current FDA approved treatments or cures for patients with Stargardt’s macular dystrophy, current research avenues include nutritional supplementation, drug therapies, and gene therapy. Case Report: A 58 year old African American female presents with suspected Stargardt’s with visual reports for comprehensive rehabilitation, including magnification assessment and genetic counseling of a patient with Stargardt’s macular dystrophy. Conclusion: Genetic testing provides insight to the phenotype and magnification determination provides significant rehabilitation to these individuals.

Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia

2020 ◽  
Author(s):  
Yousef Binamer ◽  
Muzamil A. Chisti
Keyword(s):  
Autosomal Recessive ◽  
Common Mechanism ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Skin Atrophy ◽  
Whole Exome ◽  
Infancy And Childhood ◽  
Genetics And Genomics ◽  
New Feature ◽  
Generation Sequencing

AbstractKindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of FERMT1 in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

An optometrist’s guide to the top candidate inherited retinal diseases for gene therapy

2021 ◽  
pp. 1-13
Author(s):  
Fleur O’Hare ◽  
Thomas L Edwards ◽  
Monica L Hu ◽  
Doron G Hickey ◽  
Alexis C Zhang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Retinal Diseases

Characterization of the novel HLA‐C *07:944 allele by next‐generation sequencing

HLA ◽  
2021 ◽  
Author(s):  
Maria Loginova ◽  
Olga Makhova ◽  
Daria Smirnova ◽  
Igor Paramonov ◽  
Maksim Zarubin
Keyword(s):  
Next Generation Sequencing ◽  
The Novel ◽  
Next Generation ◽  
Generation Sequencing

Characterization of the novel HLA‐B *51:296 allele by next‐generation sequencing

HLA ◽  
2020 ◽  
Author(s):  
Steve Genebrier ◽  
Vincent Elsermans ◽  
Emeric Texeraud ◽  
Gerald Bertrand ◽  
Virginie Renac
Keyword(s):  
Next Generation Sequencing ◽  
The Novel ◽  
Next Generation ◽  
Generation Sequencing

Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in the Shenzhen Population

2021 ◽  
pp. 1-7
Author(s):  
Jian Gao ◽  
Sheng Lin ◽  
Shiguo Chen ◽  
Qunyan Wu ◽  
Kaifeng Zheng ◽  
...  
Keyword(s):  
G6pd Deficiency ◽  
Amplification Refractory Mutation System ◽  
Gene Variants ◽  
Coding Region ◽  
G6pd Gene ◽  
Mutation System ◽  
Hotspot Mutations ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Generation Sequencing

<b><i>Background:</i></b> Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. This study aimed to characterize the G6PD gene variant distribution in Shenzhen of Guangdong province. <b><i>Methods:</i></b> A total of 33,562 individuals were selected at the hospital for retrospective analysis, of which 1,213 cases with enzymatic activity-confirmed G6PD deficiency were screened for G6PD gene variants. Amplification refractory mutation system PCR was first used to screen the 6 dominant mutants in the Chinese population (c.1376G&#x3e;T, c.1388G&#x3e;A, c.95A&#x3e;G, c.1024C&#x3e;T, c.392G&#x3e;T, and c.871G&#x3e;A). If the 6 hotspot variants were not found, next-generation sequencing was then performed. Finally, Sanger sequencing was used to verify all the mutations. <b><i>Results:</i></b> The incidence of G6PD deficiency in this study was 3.54%. A total of 26 kinds of mutants were found in the coding region, except for c.-8-624T&#x3e;C, which was in the noncoding region. c.1376G&#x3e;T and c.1388G&#x3e;A, both located in exon 12, were the top 2 mutants, accounting for 68.43% of all individuals. The 6 hotspot mutations had a cumulative proportion of 94.02%. <b><i>Conclusions:</i></b> This study provided detailed characteristics of G6PD gene variants in Shenzhen, and the results would be valuable to enrich the knowledge of G6PD deficiency.

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