Francesca Simonelli

Professor of Ophtalmology

Name Francesca
Surname Simonelli
Institution Università degli Studi della Campania Luigi Vanvitelli
E-Mail francesca.simonelli@unicampania.it
Address Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
Francesca Simonelli

Member PUBLICATIONS

  • A normal electro-oculography in a family affected by best disease with a novel spontaneous mutation of the BEST1 gene.

    Publication Date: 01/11/2008 on The British journal of ophthalmology
    by Testa F, Rossi S, Passerini I, Sodi A, Di Iorio V, Interlandi E, Della Corte M, Menchini U, Rinaldi E, Torricelli F, Simonelli F
    DOI: 10.1136/bjo.2008.143776

    To describe clinical and genetic findings in an Italian family affected by Best disease.

  • Safety and efficacy of gene transfer for Leber's congenital amaurosis.

    Publication Date: 22/05/2008 on The New England journal of medicine
    by Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J
    DOI: 10.1056/NEJMoa0802315

    Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.

  • Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

    Publication Date: 01/09/2007 on Investigative ophthalmology & visual science
    by Simonelli F, Ziviello C, Testa F, Rossi S, Fazzi E, Bianchi PE, Fossarello M, Signorini S, Bertone C, Galantuomo S, Brancati F, Valente EM, Ciccodicola A, Rinaldi E, Auricchio A, Banfi S
    DOI: 10.1167/iovs.07-0068

    To identify the molecular basis of Leber's congenital amaurosis (LCA) in a cohort of Italian patients and to perform genotype-phenotype analysis.

  • Intrafamilial clinical heterogeneity associated with a novel mutation of the retinal degeneration slow/peripherin gene.

    Publication Date: 01/01/2007 on Ophthalmic research
    by Simonelli F, Testa F, Marini V, Interlandi E, Rossi S, Pognuz DR, Virgili G, Garrè C, Bandello F
    DOI: 10.1159/000108118

    To identify the phenotypic variations in 6 related individuals affected by a novel mutation in the retinal degeneration slow/peripherin gene.

  • Clinical phenotype of an Italian family with a new mutation in the PRPF8 gene.

    Publication Date: 01/09/2006 on European journal of ophthalmology
    by Testa F, Ziviello C, Rinaldi M, Rossi S, Di Iorio V, Interlandi E, Ciccodicola A, Banfi S, Simonelli F

    To report the clinical and functional characteristics of an autosomal dominant retinitis pigmentosa (ADRP) family with a novel point mutation (P2301S) in the PRPF8 gene.

  • Polymorphism p.402Y>H in the complement factor H protein is a risk factor for age related macular degeneration in an Italian population.

    Publication Date: 01/09/2006 on The British journal of ophthalmology
    by Simonelli F, Frisso G, Testa F, di Fiore R, Vitale DF, Manitto MP, Brancato R, Rinaldi E, Sacchetti L
    DOI: 10.1136/bjo.2006.096487

    To evaluate the complement factor H (CFH) p.402Y>H polymorphism as a risk factor in age related macular degeneration (AMD) in an Italian population.

  • A novel mutation in the RDS gene in an Italian family with pattern dystrophy.

    Publication Date: 01/08/2005 on The British journal of ophthalmology
    by Testa F, Marini V, Rossi S, Interlandi E, Nesti A, Rinaldi M, Varano M, Garré C, Simonelli F
    DOI: 10.1136/bjo.2004.064188
  • Genotype-phenotype correlation in Italian families with Stargardt disease.

    Publication Date: 01/05/2005 on Ophthalmic research
    by Simonelli F, Testa F, Zernant J, Nesti A, Rossi S, Allikmets R, Rinaldi E
    DOI: 10.1159/000086073

    Autosomal recessive Stargardt disease (STGD) has been associated with substantial genetic and phenotypic heterogeneity. By systematic clinical analyses of STGD patients with complete genetic data (i.e. identified mutations on both alleles of the ABCA4 gene), we set out to determine phenotypic subtypes and to correlate these with specific ABCA4 alleles. Twenty-eight patients from 18 families with STGD/fundus flavimaculatus were investigated. All patients were submitted to complete ophthalmologic examination, electrophysiology, fluorescein angiography and ABCA4 gene chip analysis. Two main clinical phenotypes were observed among the examined patients. The severe phenotype was characterized by the onset of the disease <20 years and reduced ERG response, whereas the mild phenotype presented with later onset of the disease and a normal ERG response. Genetic analysis of the ABCA4 gene revealed, in the severe group, more frequently deletions, stop codons and insertions as compared to the mild phenotype group (p=0.0113 by Fisher's exact test). Moreover, the compound heterozygous mutations G1961E/5018+2T-->C found in 7 patients from 3 unrelated STGD families were associated with a mild phenotype in all subjects, except 1. This study documented variability of the clinical expression of STGD in relation to the age of onset of the disease, fundus appearance and the ERG response and allowed to subdivide patients into a severe and a mild phenotype group. These findings suggest that an extensive and comprehensive genetic analysis of STGD patients combined with thorough clinical evaluation, including the careful recording of the age of onset of the disease, would allow a more precise prognostic evaluation.

  • Association of a homozygous nonsense mutation in the ABCA4 (ABCR) gene with cone-rod dystrophy phenotype in an Italian family.

    Publication Date: 01/03/2004 on Ophthalmic research
    by Simonelli F, Testa F, Zernant J, Nesti A, Rossi S, Rinaldi E, Allikmets R
    DOI: 10.1159/000076886

    Genetic variation in the ABCA4 (ABCR) gene has been associated with several distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), retinitis pigmentosa (RP) and age-related macular degeneration. The current model of genotype/phenotype association suggests that patients harboring deleterious mutations in both ABCR alleles would develop RP-like retinal pathology. Here we describe ABCA4-associated phenotypes, including a proband with a homozygous nonsense mutation in a family from Southern Italy. The proband had been originally diagnosed with STGD. Ophthalmologic examination included kinetic perimetry, electrophysiological studies and fluorescein angiography. DNA of the affected individual and family members was analyzed for variants in all 50 exons of the ABCA4 gene by screening on the ABCR400 microarray. A homozygous nonsense mutation 2971G>T (G991X) was detected in a patient initially diagnosed with STGD based on funduscopic evidence, including bull's eye depigmentation of the fovea and flecks at the posterior pole extending to the mid-peripheral retina. Since this novel nucleotide substitution results in a truncated, nonfunctional, ABCA4 protein, the patient was examined in-depth for the severity of the disease phenotype. Indeed, subsequent electrophysiological studies determined severely reduced cone amplitude as compared to the rod amplitude, suggesting the diagnosis of CRD. ABCR400 microarray is an efficient tool for determining causal genetic variation, including new mutations. A homozygous protein-truncating mutation in ABCA4 can cause a phenotype ranging from STGD to CRD as diagnosed at an early stage of the disease. Only a combination of comprehensive genotype/phenotype correlation studies will determine the proper diagnosis and prognosis of ABCA4-associated pathology.

  • Clinical features of X linked juvenile retinoschisis associated with new mutations in the XLRS1 gene in Italian families.

    Publication Date: 01/09/2003 on The British journal of ophthalmology
    by Simonelli F, Cennamo G, Ziviello C, Testa F, de Crecchio G, Nesti A, Manitto MP, Ciccodicola A, Banfi S, Brancato R, Rinaldi E

    To describe the clinical phenotype of X linked juvenile retinoschisis in eight Italian families with six different mutations in the XLRS1 gene.