Spectrum of Disease Severity in Patients With X-Linked Retinitis Pigmentosa Due to <i>RPGR</i> Mutations

Iorio, Valentina Di; Karali, Marianthi; Melillo, Paolo; Testa, Francesco; Brunetti-Pierri, Raffaella; Musacchia, Francesco; Condroyer, Christel; Neidhardt, John; Audo, Isabelle; Zeitz, Christina; Banfi, Sandro; Simonelli, Francesca

doi:10.1167/iovs.61.14.36

Cited by 23 publications

(45 citation statements)

References 79 publications

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“…MP was performed by an automatic fundus-related perimeter (MP1 Microperimeter, Nidek Technologies, Padova, Italy). The following parameters were used: a fixation target of 2 degrees in diameter consisting of a red ring; a white, monochromatic background with a luminance of 1.27 cd/m 2 ; a Goldmann III-size stimulus with a projection time of 200 ms; a predefined automatic test pattern (Humphrey 10-2) covering 10 degrees centered onto the gravitational center of the fixation points with 68 stimuli [40].…”

Section: Ophthalmological Examinationmentioning

confidence: 99%

Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study

Brunetti-Pierri

Karali

Melillo

et al. 2021

IJMS

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Achromatopsia (ACHM) is a rare genetic disorder of infantile onset affecting cone photoreceptors. To determine the extent of progressive retinal changes in achromatopsia, we performed a detailed longitudinal phenotyping and genetic characterization of an Italian cohort comprising 21 ACHM patients (17 unrelated families). Molecular genetic testing identified biallelic pathogenic mutations in known ACHM genes, including four novel variants. At baseline, the patients presented a reduced best corrected visual acuity (BCVA), reduced macular sensitivity (MS), normal dark-adapted electroretinogram (ERG) responses and undetectable or severely reduced light-adapted ERG. The longitudinal analysis of 16 patients (mean follow-up: 5.4 ± 1.0 years) showed a significant decline of BCVA (0.012 logMAR/year) and MS (−0.16 dB/year). Light-adapted and flicker ERG responses decreased below noise level in three and two patients, respectively. Only two patients (12.5%) progressed to a worst OCT grading during the follow-up. Our findings corroborate the notion that ACHM is a progressive disease in terms of BCVA, MS and ERG responses, and affects slowly the structural integrity of the retina. These observations can serve towards the development of guidelines for patient selection and intervention timing in forthcoming gene replacement therapies.

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Section: Ophthalmological Examinationmentioning

confidence: 99%

Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study

Brunetti-Pierri

Karali

Melillo

et al. 2021

IJMS

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“…This makes pathogenic variants in this gene the third most-prevalent cause of IRDs in this population [ 82 ]. In an Italian cohort of 48 RPGR -related RP cases, approximately half had mutations in ORF15 and presented with a more severe phenotype than the other causative variants in exons 1–14 of RPGR [ 107 ]. It has been suggested that the sequence coverage of ORF15 could be optimised by modifying NGS library preparation, reducing false-negatives, miscalled variants and false-positives when compared to traditional methods [ 108 ].…”

Section: Expanding Ird Diagnosis Via Whole-gene or Wgsmentioning

confidence: 99%

Next-Generation Sequencing Applications for Inherited Retinal Diseases

Dockery

Whelan

Humphries

et al. 2021

IJMS

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Inherited retinal diseases (IRDs) represent a collection of phenotypically and genetically diverse conditions. IRDs phenotype(s) can be isolated to the eye or can involve multiple tissues. These conditions are associated with diverse forms of inheritance, and variants within the same gene often can be associated with multiple distinct phenotypes. Such aspects of the IRDs highlight the difficulty met when establishing a genetic diagnosis in patients. Here we provide an overview of cutting-edge next-generation sequencing techniques and strategies currently in use to maximise the effectivity of IRD gene screening. These techniques have helped researchers globally to find elusive causes of IRDs, including copy number variants, structural variants, new IRD genes and deep intronic variants, among others. Resolving a genetic diagnosis with thorough testing enables a more accurate diagnosis and more informed prognosis and should also provide information on inheritance patterns which may be of particular interest to patients of a child-bearing age. Given that IRDs are heritable conditions, genetic counselling may be offered to help inform family planning, carrier testing and prenatal screening. Additionally, a verified genetic diagnosis may enable access to appropriate clinical trials or approved medications that may be available for the condition.

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“…It is located at the position Xp11.4. [ 223 ] RPGR is associated with 80% of XLRP cases, 10%–20% of cases of familial RP, and 12%–15% of all the sporadic cases. It is made up of 22 exons that encode for the RPGR protein.…”

Section: Gtpase Regulator Gene For Retinitis Pigmentosamentioning

confidence: 99%

Genetic dissection of non-syndromic retinitis pigmentosa

Bhardwaj

Yadav

et al. 2022

Indian Journal of Ophthalmology

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Retinitis pigmentosa (RP) belongs to a group of pigmentary retinopathies. It is the most common form of inherited retinal dystrophy, characterized by progressive degradation of photoreceptors that leads to nyctalopia, and ultimately, complete vision loss. RP is distinguished by the continuous retinal degeneration that progresses from the mid-periphery to the central and peripheral retina. RP was first described and named by Franciscus Cornelius Donders in the year 1857. It is one of the leading causes of bilateral blindness in adults, with an incidence of 1 in 3000 people worldwide. In this review, we are going to focus on the genetic heterogeneity of this disease, which is provided by various inheritance patterns, numerosity of variations and inter-/intra-familial variations based upon penetrance and expressivity. Although over 90 genes have been identified in RP patients, the genetic cause of approximately 50% of RP cases remains unknown. Heterogeneity of RP makes it an extremely complicated ocular impairment. It is so complicated that it is known as “fever of unknown origin”. For prognosis and proper management of the disease, it is necessary to understand its genetic heterogeneity so that each phenotype related to the various genetic variations could be treated.

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Spectrum of Disease Severity in Patients With X-Linked Retinitis Pigmentosa Due to RPGR Mutations

Cited by 23 publications

References 79 publications

Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study

Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study

Next-Generation Sequencing Applications for Inherited Retinal Diseases

Genetic dissection of non-syndromic retinitis pigmentosa

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