Elsevier

Ophthalmology

Volume 121, Issue 12, December 2014, Pages 2406-2414
Ophthalmology

Original article
Frequency and Clinical Pattern of Vitelliform Macular Dystrophy Caused by Mutations of Interphotoreceptor Matrix IMPG1 and IMPG2 Genes

Presented as a poster at: American Academy of Ophthalmology Annual Meeting, November 2013, New Orleans, Louisiana.
https://doi.org/10.1016/j.ophtha.2014.06.028Get rights and content

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.

Section snippets

Methods

The DNA repository of the Maolya Outpatient Clinic for Genetic Sensory Diseases (Montpellier University Hospital, Montpellier, France) was screened for families with vitelliform macular dystrophy. Informed consent was obtained for clinical examination and genetic analysis from all patients in agreement with the principles of the Declaration of Helsinki. We also obtained ethical approval from the Montpellier University Hospital.

Results

Seventy-six families had a vitelliform dystrophy. Among the 45 families with an age of onset before 40 years, 24 had a mutation in BEST1, and among the 31 families with an age of onset older than 40 years, 3 had a mutation in PRPH2. For the 49 families without identified mutations, 3 families were found to have a mutation in IMPG1 (6% of included families, 11 patients; Fig 1, available at www.aaojournal.org) and 1 family was found to have a mutation in IMPG2 (2% of included families, 2

Discussion

The aim of the present study was to evaluate the frequency and the relevant clinical and SD-OCT findings of IMPG1 and IMPG2 vitelliform dystrophies in patients for whom exonic mutations or rearrangements in BEST1 and PRPH2 had been excluded. It should be pointed out that deep intronic mutations were not screened. IMPG1 was associated more frequently with such a phenotype in comparison with IMPG2. Nevertheless, these 2 genes account for a small proportion of cases: 4 families among the 49

References (31)

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    Citation Excerpt :

    These post-translational modifications (PTMs) are believed to be important for binding other IPM constituents, stabilizing the matrix, and supporting the growth and maintenance of OS (Chen et al., 2004). Mutations in IMPG2 cause multiple retinal pathologies, including a severe form of autosomal recessive RP that also affects the cone photoreceptor-rich macula early in the course of the disease, leading to irreversible vision loss in childhood (Bandah-Rozenfeld et al., 2010; Bocquet et al., 2013; Brandl et al., 2017; Huet et al., 2014; Khan and Al Teneiji, 2019; Meunier et al., 2014). Structurally, noninvasive imaging of affected patients by optical coherence tomography shows a reduction in retinal thickness and a loss of outer retinal bands corresponding to the photoreceptor OS layer (Brandl et al., 2017; Khan and Al Teneiji, 2019).

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Supplemental material is available at www.aaojournal.org.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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