Macular Dystrophy/Stargardt Disease

Gene: IMPG1

Green List (high evidence)

- Manes, et al. 2013 (PMID: 23993198) identified 3 families with autosomal dominant vitelliform macular dystrophy (VMD), associated with a recurrent c.713T>G variant leading to p.Leu238Arg in IMPG1. Screening of IMPG1 in a cohort of VMD patients revealed 2 further families with either homozygous for the c.807+1G>T splice-site variant, or compound heterozygous for variants c.461T>C (p.Leu154Pro) and c.1519C>T (p.Arg507(∗)).

- Brandl et al. 2017 (PMID: 28644393) identified 2 unrelated childhood-onset VMD cases with a heterozygous c.713T>C (p.Leu238Pro) missense variant and a homozygous c.807+5G>A splice-site variant, respectively.

- González-Gómez et al. 2019 (PMID: 30589393) reported on a 41-year-old woman with gradual bilateral decrease of her visual acuity due to bull's eye maculopathy. Sequencing identified a heterozygous variant c.121+2T>C in the IMPG1 gene.

- Gupta et al. 2019 (PMID: 30688845) describe a 25-year-old female patient with symptomatic scotoma and vision decrease. Multifocal electroretinogram revealed slightly decreased retinal sensitivity in the central retina of the left eye. Genetic testing identified a heterozygous p.Leu154Pro mutation in the IMPG1 gene.

- Olivier et al. 2021 (PMID: 32817297) identified seven variants in IMPG1 (including five novel) in 11 families with VMD or retinitis pigmentosa (RP). 4 families were diagnosed with autosomal dominant RP, 2 families had autosomal recessive RP, while 5 families developed VMD in association with heterozygous IMPG1 variants. Notably, inter- and intrafamilial phenotypic variation was evident with some individuals presenting RP while others had VMD, despite harbouring the same IMPG1 variant. Knockdown of Impg1 in medaka fish resulted in a phenotype consistent with that observed in human patients, including a decreased length of rod and cone photoreceptor outer segments.
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Notably, asymptomatic heterozygous carriers of IMPG1 variants with normal clinical examinations have been observed (PMIDs: 23993198 and 32817297) indicating incomplete penetrance.

Created: 7 Aug 2021, 1:30 a.m. | Last Modified: 7 Aug 2021, 1:30 a.m.

Panel Version: 0.27

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Macular dystrophy, vitelliform, 4, OMIM:616151; Retinitis pigmentosa, MONDO:0019200

Publications

• 23993198
• 28644393
• 30589393
• 30688845
• 32817297