title: Hypotrichosis and juvenile macular dystrophy caused by CDH3 mutation: A candidate disease for retinal gene therapy.
abstract: Hypotrichosis with juvenile macular dystrophy (HJMD) is an autosomal recessive disorder that causes childhood visual impairment. HJMD is caused by mutations in CDH3 which encodes cadherin-3, a protein expressed in retinal pigment epithelium (RPE) cells that may have a key role in intercellular adhesion. We present a case of HJMD and analyse its phenotypic and molecular characteristics to assess the potential for retinal gene therapy as a means of preventing severe visual loss in this condition. Longitudinal in vivo imaging of the retina showed the relative anatomical preservation of the macula, which suggested the presence of a therapeutic window for gene augmentation therapy to preserve visual acuity. The coding sequence of CDH3 fits within the packaging limit of recombinant adeno-associated virus vectors that have been shown to be safe in clinical trials and can efficiently target RPE cells. This report expands the number of reported cases of HJMD and highlights the phenotypic characteristics to consider when selecting candidates for retinal gene therapy.
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.|Moorfields Eye Hospital NHS Foundation Trust and NIHR Ophthalmology Biomedical Research Centre, London, UK.
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Singh
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Broadgate
authors.affiliation: Singapore National Eye Centre and Singapore Eye Research Institute, Singapore.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Mathur
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Holt
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Halford
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.|Oxford Eye Hospital, Oxford University Hospitals NHS Trust and NIHR Biomedical Research Centre, Oxford, UK.|Moorfields Eye Hospital NHS Foundation Trust and NIHR Ophthalmology Biomedical Research Centre, London, UK.
authors.forename: Robert E
authors.initials: RE
authors.lastname: MacLaren
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D002648:Child; D000229:Dependovirus / Q000235:genetics; D005091:Exons; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics* / Q000473:pathology; D008268:Macular Degeneration / Q000151:congenital* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008297:Male; D016254:Mutagenesis, Insertional; D012160:Retina / Q000033:anatomy & histology / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence; D014792:Visual Acuity
chemical_list: C512197:CDH3 protein, human; D015820:Cadherins