title: Frequency and clinical pattern of vitelliform macular dystrophy caused by mutations of interphotoreceptor matrix IMPG1 and IMPG2 genes.
abstract: OBJECTIVE
  To assess the frequency of and to characterize the clinical spectrum and optical coherence tomography findings of vitelliform macular dystrophy linked to IMPG1 and IMPG2, 2 new causal genes expressed in the interphotoreceptor matrix.
  
  
  METHODS
  Retrospective epidemiologic, clinical, electrophysiologic, and molecular genetic study.
  
  
  METHODS
  The database of a national referral center specialized in genetic sensory diseases was screened for patients with a macular vitelliform dystrophy without identified mutation or small deletion or large rearrangement in BEST1 and PRPH2 genes. Forty-nine families were included.
  
  
  METHODS
  Clinical, imaging, and electro-oculogram findings were reviewed. Mutation screening of IMPG1 and IMPG2 genes were performed systematically.
  
  
  METHODS
  Frequency, inheritance, and clinical pattern of vitelliform dystrophy associated with IMPG1 and IMPG2 mutations were characterized.
  
  
  RESULTS
  IMPG1 was the causal gene in 3 families (IMPG1 1-3, 11 patients) and IMPG2 in a fourth family (2 patients). With an autosomal dominant transmission, families 1 and 2 had the c.713T→G (p.Leu238Arg) mutation in IMPG1 and family 4 had the c.3230G→T (p.Cys1077Phe) mutation in IMPG2. Patients with IMPG1 or IMPG2 mutations had a late onset and moderate visual impairment (mean visual acuity, 20/40; mean age of onset, 42 years), even in the sporadic case of family 3 with a presumed recessive transmission (age at onset, 38 years; mean visual acuity, 20/50). Drusen-like lesions adjacent to the vitelliform deposits were observed in 9 of 13 patients. The vitelliform material was above the retinal pigment epithelium (RPE) at any stage of the macular dystrophy, and this epithelium was well preserved and maintained its classical reflectivity on spectral-domain optical coherence tomography (SD-OCT). Electro-oculogram results were normal or borderline in 9 cases.
  
  
  CONCLUSIONS
  IMPG1 and IMPG2 are new causal genes in 8% of families negative for BEST1 and PRPH2 mutations. These genes should be screened in adult-onset vitelliform dystrophy with (1) moderate visual impairment, (2) drusen-like lesions, (3) normal reflectivity of the RPE line on SD-OCT, and (4) vitelliform deposits located between ellipsoid and interdigitation lines on SD-OCT. These clinical characteristics are not observed in the classical forms of BEST1 or PRPH2 vitelliform dystrophies.
authors.affiliation: Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University, Montpellier, France; Institute for Neurosciences, INSERM, Montpellier, France. Electronic address: isabelannemeunier@yahoo.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.affiliation: Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Institute for Neurosciences, INSERM, Montpellier, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Manes
authors.affiliation: Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University, Montpellier, France; Institute for Neurosciences, INSERM, Montpellier, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bocquet
authors.affiliation: Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University, Montpellier, France; Institute for Neurosciences, INSERM, Montpellier, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Marquette
authors.affiliation: Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University, Montpellier, France; Institute for Neurosciences, INSERM, Montpellier, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Baudoin
authors.affiliation: Service d'Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, Lille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Puech
authors.affiliation: Service d'Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, Lille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Defoort-Dhellemmes
authors.affiliation: Service d'Ophtalmologie, Centre National des XV-XX, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
authors.affiliation: Ophthalmologist, Avignon, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Verdet
authors.affiliation: Eye Clinic, Hôpital Robert Debré, Reims, France.
authors.forename: Carl
authors.initials: C
authors.lastname: Arndt
authors.affiliation: Clinic Sourdille, Nantes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Zanlonghi
authors.affiliation: Service d'Ophtalmologie, Centre Hospitalier Universitaire, Nantes, France.
authors.forename: Guylène
authors.initials: G
authors.lastname: Le Meur
authors.affiliation: Institut de Biochimie et Biologie Moléculaire, UF Génopathies, Lille, France, and Université Lille Nord de France, Lille, France.
authors.forename: Claire-Marie
authors.initials: CM
authors.lastname: Dhaenens
authors.affiliation: Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University, Montpellier, France; Institute for Neurosciences, INSERM, Montpellier, France.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004585:Electrooculography; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011509:Proteoglycans / Q000235:genetics*; D055213:Retinal Pigment Epithelium / Q000473:pathology; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D057826:Vitelliform Macular Dystrophy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; C486428:IMPG1 protein, human; C412522:IMPG2 protein, human; D011509:Proteoglycans