Frequency and clinical pattern of vitelliform macular dystrophy caused by mutations of interphotoreceptor matrix IMPG1 and IMPG2 genes

  • Ophthalmology. 2014 Dec;121(12):2406-14. doi: 10.1016/j.ophtha.2014.06.028.
Isabelle Meunier  1 ,  Gaël Manes  2 ,  Béatrice Bocquet  3 ,  Virginie Marquette  3 ,  Corinne Baudoin  3 ,  Bernard Puech  4 ,  Sabine Defoort-Dhellemmes  4 ,  Isabelle Audo  5 ,  Robert Verdet  6 ,  Carl Arndt  7 ,  Xavier Zanlonghi  8 ,  Guylène Le Meur  9 ,  Claire-Marie Dhaenens  10 ,  Christian P Hamel  3
Affiliations
  • 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: [email protected].
  • 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.
PMID: 25085631 DOI: 10.1016/j.ophtha.2014.06.028
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.