Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy
Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age r...
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doaj-5a40854b9950463c9143105ae0b934382020-11-24T22:28:09ZengHindawi LimitedJournal of Ophthalmology2090-004X2090-00582017-01-01201710.1155/2017/30802453080245Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative VitreoretinopathyGiancarlo Iarossi0Matteo Bertelli1Paolo Enrico Maltese2Elena Gusson3Giorgio Marchini4Alice Bruson5Sabrina Benedetti6Sabrina Volpetti7Gino Catena8Luca Buzzonetti9Lucia Ziccardi10Department of Ophthalmology, Bambino Gesù IRCCS Children's Hospital, Rome, ItalyMAGI-Human Medical Genetics Institute, Bolzano, ItalyMAGI-Human Medical Genetics Institute, Rovereto, ItalyEye Clinic, Department of Neurosciences, Biomedicine and Movement, University and AOUI (Azienda Ospedaliera Universitaria Integrata) of Verona, Verona, ItalyEye Clinic, Department of Neurosciences, Biomedicine and Movement, University and AOUI (Azienda Ospedaliera Universitaria Integrata) of Verona, Verona, ItalyMAGI-Human Medical Genetics Institute, Rovereto, ItalyMAGI-Human Medical Genetics Institute, Rovereto, ItalyDipartimento Anestesia e Rianimazione Materno Infantile, Ospedale San Filippo Neri, Rome, ItalyDepartment of Ophthalmology, Bambino Gesù IRCCS Children's Hospital, Rome, ItalyDepartment of Ophthalmology, Bambino Gesù IRCCS Children's Hospital, Rome, Italy“G.B. Bietti” Foundation, IRCCS, Rome, ItalyFamilial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7–19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.http://dx.doi.org/10.1155/2017/3080245 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giancarlo Iarossi Matteo Bertelli Paolo Enrico Maltese Elena Gusson Giorgio Marchini Alice Bruson Sabrina Benedetti Sabrina Volpetti Gino Catena Luca Buzzonetti Lucia Ziccardi |
spellingShingle |
Giancarlo Iarossi Matteo Bertelli Paolo Enrico Maltese Elena Gusson Giorgio Marchini Alice Bruson Sabrina Benedetti Sabrina Volpetti Gino Catena Luca Buzzonetti Lucia Ziccardi Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy Journal of Ophthalmology |
author_facet |
Giancarlo Iarossi Matteo Bertelli Paolo Enrico Maltese Elena Gusson Giorgio Marchini Alice Bruson Sabrina Benedetti Sabrina Volpetti Gino Catena Luca Buzzonetti Lucia Ziccardi |
author_sort |
Giancarlo Iarossi |
title |
Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy |
title_short |
Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy |
title_full |
Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy |
title_fullStr |
Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy |
title_full_unstemmed |
Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy |
title_sort |
genotype-phenotype characterization of novel variants in six italian patients with familial exudative vitreoretinopathy |
publisher |
Hindawi Limited |
series |
Journal of Ophthalmology |
issn |
2090-004X 2090-0058 |
publishDate |
2017-01-01 |
description |
Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7–19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family. |
url |
http://dx.doi.org/10.1155/2017/3080245 |
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