title: Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing.
abstract: To assess the clinical utility of targeted Next-Generation Sequencing (NGS) for the diagnosis of Inherited Retinal Dystrophies (IRDs), a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Stargardt Disease (STGD), Best Macular Dystrophy (BMD), Usher Syndrome (USH), and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS). Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.
authors.affiliation: Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Isabella
authors.identifier: 0000-0001-9032-8197
authors.initials: I
authors.lastname: Bernardis
authors.affiliation: Institute of Ophthalmology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Laura
authors.identifier: 0000-0002-1801-0958
authors.initials: L
authors.lastname: Chiesi
authors.affiliation: Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tenedini
authors.affiliation: Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Artuso
authors.affiliation: Medical Genetics Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Percesepe
authors.affiliation: Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Artusi
authors.affiliation: Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy; Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Simone
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; Centre for Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Manfredini
authors.affiliation: Ophthalmology, S.Bi.Bi.T. Department, University of Parma, Parma, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Camparini
authors.affiliation: Ophthalmology, S.Bi.Bi.T. Department, University of Parma, Parma, Italy.
authors.forename: Chiara
authors.identifier: 0000-0001-9958-9406
authors.initials: C
authors.lastname: Rinaldi
authors.affiliation: Ophthalmology Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ciardella
authors.affiliation: Medical Genetics Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Graziano
authors.affiliation: Ophthalmology Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Nicole
authors.identifier: 0000-0002-2625-2244
authors.initials: N
authors.lastname: Balducci
authors.affiliation: Medical Genetics Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Antonia
authors.identifier: 0000-0002-8238-7776
authors.initials: A
authors.lastname: Tranchina
authors.affiliation: Institute of Ophthalmology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Gian Maria
authors.identifier: 0000-0003-0914-2884
authors.initials: GM
authors.lastname: Cavallini
authors.affiliation: Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Pietrangelo
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Marigo
authors.affiliation: Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Enrico
authors.identifier: 0000-0003-0981-2542
authors.initials: E
authors.lastname: Tagliafico
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005817:Genetic Counseling / Q000379:methods; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D057089:Pathology, Molecular / Q000379:methods; D010375:Pedigree; D058499:Retinal Dystrophies / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics; D055815:Young Adult
chemical_list: D005136:Eye Proteins