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. Epub 2014 Jul 29.


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.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Electrooculography
  • Extracellular Matrix Proteins / genetics*
  • Eye Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Proteoglycans / genetics*
  • Retinal Pigment Epithelium / pathology
  • Retrospective Studies
  • Tomography, Optical Coherence
  • Visual Acuity
  • Vitelliform Macular Dystrophy* / genetics
  • Vitelliform Macular Dystrophy* / pathology
  • Vitelliform Macular Dystrophy* / physiopathology


  • Extracellular Matrix Proteins
  • Eye Proteins
  • IMPG1 protein, human
  • IMPG2 protein, human
  • Proteoglycans