Dataset Information

Clinical and Genetic Analysis of a European Cohort with Pericentral Retinitis Pigmentosa.

ABSTRACT: Retinitis pigmentosa (RP) is a clinically heterogenous disease that comprises a wide range of phenotypic and genetic subtypes. Pericentral RP is an atypical form of RP characterized by bone-spicule pigmentation and/or atrophy confined in the near mid-periphery of the retina. In contrast to classic RP, the far periphery is better preserved in pericentral RP. The aim of this study was to perform the first detailed clinical and genetic analysis of a cohort of European subjects with pericentral RP to determine the phenotypic features and the genetic bases of the disease. A total of 54 subjects from 48 independent families with pericentral RP, non-syndromic and syndromic, were evaluated through a full ophthalmological examination and underwent clinical exome or retinopathy gene panel sequencing. Disease-causative variants were identified in 22 of the 35 families (63%) in 10 different genes, four of which are also responsible for syndromic RP. Thirteen of the 34 likely pathogenic variants were novel. Intra-familiar variability was also observed. The current study confirms the mild phenotype of pericentral RP and extends the spectrum of genes associated with this condition.

SUBMITTER: Karali M

PROVIDER: S-EPMC6982348 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Clinical and Genetic Analysis of a European Cohort with Pericentral Retinitis Pigmentosa.

Karali Marianthi M Testa Francesco F Brunetti-Pierri Raffaella R Di Iorio Valentina V Pizzo Mariateresa M Melillo Paolo P Barillari Maria Rosaria MR Torella Annalaura A Musacchia Francesco F D'Angelo Luigi L Banfi Sandro S Simonelli Francesca F

International journal of molecular sciences 20191220 1

Retinitis pigmentosa (RP) is a clinically heterogenous disease that comprises a wide range of phenotypic and genetic subtypes. Pericentral RP is an atypical form of RP characterized by bone-spicule pigmentation and/or atrophy confined in the near mid-periphery of the retina. In contrast to classic RP, the far periphery is better preserved in pericentral RP. The aim of this study was to perform the first detailed clinical and genetic analysis of a cohort of European subjects with pericentral RP t ...[more]

PMID: 31877679

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Project description:BackgroundPanel-based targeted exome sequencing was applied to identify the pathogenic variants and genetic characteristics of retinitis pigmentosa (RP) in two Chinese families, and to gain a deeper understanding of the relationship between clinical manifestations and genotypes.MethodsA total of 17 subjects, comprising two probands (total patients: four subjects) and their family member, were recruited in this study. All subjects underwent comprehensive ophthalmic examinations and clinical evaluations, and the complete history and medical records were collected according to the standard procedures. All participants were screened using the multigene panel test (Target_Eye_792_V2 chip), and Sanger sequencing was used to confirm the candidate variants.ResultsAmong these two families, a total of three novel mutations in the EYS gene were identified in patients, including a homozygous frameshift mutation c.9252_9253insT detected in two patients in one family, and the compound heterozygous splicesite mutation c.5644+2T>C and frameshift mutation c.1920_1923delTGAG detected in two patients in the another family. All patients in both families had early onset of night blindness and poor visual acuity, and with typical posterior capsule opacification. The mutation co-segregated within all recruited individuals. In addition, one patient with compound heterozygous mutations was found to have typical blue-blindness symptoms and detected a previously reported disease-causing mutation c.235G>A in OPN1SW gene, which caused blue blindness manifestations and was first discovered in patient combined with RP causative genes.ConclusionsPanel-based targeted exome sequencing was used to identify three novel variants of RP causative gene, and we also detected a known pathogenic variants of blue-blindness causative genes in two patients. Our finding will provide a powerful basis for genetic counseling and enhance our current understanding of the genetics factors for RP families.

Project description:BACKGROUND:Panel-based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa. METHODS:A total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with confirmed retinitis pigmentosa were recruited in the study. Panel-based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination. RESULTS:Of the 23 probands, the clinical manifestations include night blindness, narrowing of vision, secondary cataracts, choroidal atrophy, color blindness, and high myopia, the average age of onset of night blindness is 12.9 ± 14 (range, 0-65; median, 8). Posterior subcapsular opacities is the most common forms of secondary cataracts (nine cases, 39.1%), and peripheral choroidal atrophy is the most common form of secondary choroidal atrophy (12 cases, 52.2%). Of these probands with complication peripheral choroidal atrophy, there were eight probands (66.7%, 8/12) caused by the pathogenic variation in USH2A gene. A total of 17 genes and 45 variants were detected in 23 probands. Among these genes, the commonest genes were USH2A (40%; 18/45), RP1 (15.6%; 7/45), and EYS (8.9%; 4/45), and the top three genes account for 56.5% (13/23) of diagnostic probands. Among these variants, comprising 22 (48.9%) pathogenic variants, 14 (31%) likely pathogenic variants, and nine (20%) uncertain clinical significance variants, and 22 variants was discovered first time. Most of the mutations associated with RP were missense (53.3%, 24/45), and the remaining mutation types include frameshift (35.6%, 16/45), nonsense (6.7%, 3/45), and spliceSite (4.4%, 2/45). Among the probands with mutations detected, compound heterozygous forms was detected in 13 (56.5%, 13/23) probands, and digenic inheritance (DI) forms was detected in five (21.7%, 5/23) probands. CONCLUSION:Panel-based targeted exome sequencing revealed 23 novel mutations, recognized different combinations forms of variants, and extended the mutational spectrum of retinitis pigmentosa and depicted common variants in northeast China.

Dataset Information

Clinical and Genetic Analysis of a European Cohort with Pericentral Retinitis Pigmentosa.

Publications

Clinical and Genetic Analysis of a European Cohort with Pericentral Retinitis Pigmentosa.

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