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Additional file 5: Table S5. Assessment of surgical strategy. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to surgery for IRD.

Additional file 4: Table S4. Patient eligibility and prioritisation. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to patient identification and prioritisation of treatment.

Additional file 6: Appendix. Members of the panel of experts. List of all members of the panel of experts who participated in the Delphi consensus process.

Additional file 4: Table S4. Patient eligibility and prioritisation. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to patient identification and prioritisation of treatment.

Additional file 1: Table S1. Clinical manifestations of RPE65-associated IRD. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to the clinical manifestations of RPE65.

Additional file 3: Table S3. Genetic testing. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to genetic testing for IRD.

Additional file 6: Appendix. Members of the panel of experts. List of all members of the panel of experts who participated in the Delphi consensus process.

Additional file 3: Table S3. Genetic testing. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to genetic testing for IRD.

Additional file 2: Table S2. Viable retinal cells: structure and function. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to the structure and function of retinal cells.

Additional file 2: Table S2. Viable retinal cells: structure and function. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to the structure and function of retinal cells.

Additional file 1.

Additional file 5: Table S5. Assessment of surgical strategy. Provides an overview of the consensus during the Round 1 and Round 2 questionnaires on statements relating to surgery for IRD.

Inherited retinal diseases (IRDs) are the leading cause of vision loss in the working-age population. We performed a retrospective epidemiological study to determine the genetic basis of IRDs in a large Italian cohort (n = 2790) followed at a single referral center. We provided, mainly by next generation sequencing, potentially conclusive molecular diagnosis for 2036 patients (from 1683 unrelated families). We identified a total of 1319 causative sequence variations in 132 genes, including 353 novel variants, and 866 possibly actionable genotypes for therapeutic approaches. ABCA4 was the most frequently mutated gene (n = 535; 26.3% of solved cases), followed by USH2A (n = 228; 11.2%) and RPGR (n = 102; 5.01%). The other 129 genes had a lower contribution to IRD pathogenesis (e.g. CHM 3.5%, RHO 3.5%; MYO7A 3.4%; CRB1 2.7%; RPE65 2%, RP1 1.8%; GUCY2D 1.7%). Seventy-eight genes were mutated in five patients or less. Mitochondrial DNA variants were responsible for 2.1% of cases. Our analysis confirms the complex genetic etiology of IRDs and reveals the high prevalence of ABCA4 and USH2A mutations. This study also uncovers genetic associations with a spectrum of clinical subgroups and highlights a valuable number of cases potentially eligible for clinical trials and, ultimately, for molecular therapies.

Background An increasing number of patients have been described as having a number of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) variants for which it lacks a clear genotype–phenotype correlation. We assesses the clinical features of patients bearing the S737F (p.Ser737Phe) CFTR missense variant and evaluated the residual function of CFTR protein on nasal epithelial cells (NEC). Methods A retrospective database was performed from individuals homozygous or compound heterozygous for the S737F variant followed in the Cystic Fibrosis (CF) Centre of Florence. We performed a nasal brushing in cooperating patients and compared the results with those of patients followed in the pediatric CF Centre of Naples. Results 9/295 (3%) subjects carrying at least S737F CFTR variant on one allele were identified. Patients were diagnosed in 7/9 cases by newborn screening and in two cases for dehydration with hypochloremic metabolic alkalosis; at diagnosis sweat chloride levels (SCL) were in the pathological range in only one case. After a mean follow up of 8,6 years (range 0,5–15,8), SCL were in the pathological range in 8/9 cases (mean age at CF diagnosis: 1,5 years), all patients were pancreatic sufficiency and respiratory function was normal. The gating activity on NEC was 15.6% and 12.7% in two patients compound heterozygous for W1282X and DelE22_24, while it was ranged between 6,2% and 9,8% in CF patients. Conclusions S737F is a CFTR mutation associated to hypochloremic alkalosis in childhood, mild CF phenotype in teenage years and a residual function of CFTR protein.