Isabelle Meunier1, Gaël Manes2, Béatrice Bocquet3, Virginie Marquette3, Corinne Baudoin3, Bernard Puech4, Sabine Defoort-Dhellemmes4, Isabelle Audo5, Robert Verdet6, Carl Arndt7, Xavier Zanlonghi8, Guylène Le Meur9, Claire-Marie Dhaenens10, Christian P Hamel3. 1. 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. 2. Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Institute for Neurosciences, INSERM, Montpellier, France. 3. Centre de Référence Maladies Sensorielles Génétiques, Hôpital Gui de Chauliac, Montpellier, France; Montpellier University, Montpellier, France; Institute for Neurosciences, INSERM, Montpellier, France. 4. Service d'Exploration de la Vision et Neuro-ophtalmologie, Hôpital Robert Salengro, Lille, France. 5. Service d'Ophtalmologie, Centre National des XV-XX, Paris, France. 6. Ophthalmologist, Avignon, France. 7. Eye Clinic, Hôpital Robert Debré, Reims, France. 8. Clinic Sourdille, Nantes, France. 9. Service d'Ophtalmologie, Centre Hospitalier Universitaire, Nantes, France. 10. Institut de Biochimie et Biologie Moléculaire, UF Génopathies, Lille, France, and Université Lille Nord de France, Lille, France.
Abstract
PURPOSE: 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. DESIGN: Retrospective epidemiologic, clinical, electrophysiologic, and molecular genetic study. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
PURPOSE: 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. DESIGN: Retrospective epidemiologic, clinical, electrophysiologic, and molecular genetic study. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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 PRPH2vitelliform dystrophies.
Authors: Adiv A Johnson; Karina E Guziewicz; C Justin Lee; Ravi C Kalathur; Jose S Pulido; Lihua Y Marmorstein; Alan D Marmorstein Journal: Prog Retin Eye Res Date: 2017-01-30 Impact factor: 21.198
Authors: Karina E Guziewicz; Divya Sinha; Néstor M Gómez; Kathryn Zorych; Emily V Dutrow; Anuradha Dhingra; Robert F Mullins; Edwin M Stone; David M Gamm; Kathleen Boesze-Battaglia; Gustavo D Aguirre Journal: Prog Retin Eye Res Date: 2017-01-19 Impact factor: 21.198
Authors: Caroline Brandl; Heidi L Schulz; Peter Charbel Issa; Johannes Birtel; Richard Bergholz; Clemens Lange; Claudia Dahlke; Ditta Zobor; Bernhard H F Weber; Heidi Stöhr Journal: Genes (Basel) Date: 2017-06-23 Impact factor: 4.096
Authors: Robert A Sisk; Robert B Hufnagel; Ailee Laham; Elizabeth S Wohler; Nara Sobreira; Zubair M Ahmed Journal: J Ophthalmol Date: 2018-07-11 Impact factor: 1.909