Co-inheritance of the membrane frizzled-related protein ocular phenotype and glycogen storage disease type Ib

ABSTRACT

Aim: To report co-occurrence of two rare recessive conditions, the membrane frizzled-related protein (MFRP)-related ocular phenotype and glycogen storage disease type 1b (GSD-1b), in three siblings in an Omani family.

Background: Biallelic mutations in the MFRP gene (chromosome 11q23) result in a distinct ocular phenotype characterized by retinitis pigmentosa, foveoschisis, optic nerve head drusen, and posterior microphthalmos. GSD-1b is an autosomal-recessive disorder caused by mutations in SLC37A4 gene located in the same chromosomal region.

Methods: An Omani family with three siblings diagnosed with GSD-1b presented with ocular manifestations of progressive visual impairment and diminution of night vision. All siblings underwent a standard ophthalmic and clinical genetic evaluation. Full sequencing of the MFRP and SLC37A4 genes and haplotype analysis was carried out.

Results: The three children (2F:1M) aged 13, 17, and 18 years were born to consanguineous parents. Their best-corrected visual acuity ranged from 20/60 to 20/15. Ophthalmic exam revealed bilateral optic disc drusen, foveoschisis, and pigmentary retinopathy, hyperopia of +12 to +15.5 diopters, and decreased axial length (15.8–16.39 mm) in all affected siblings. Full-field electroretinography showed rod-cone dysfunction. Sequence analysis revealed two novel variants in a homozygous state in the SLC37A4 and MFRP genes in all the affected patients.

Conclusions: We report the MFRP-related ocular phenotype in three siblings with GSD-1b. Molecular genetic studies identified novel mutations in the MFRP and SLC37A4 genes. Co-inheritance of a haplotype harboring mutations in both loci on chromosome 11q23 resulted in co-occurrence of the MFRP-related ocular phenotype and GSD-1b. This has not been reported previously.

KEYWORDS:

• Coinheritance
• foveoschisis
• glycogen storage disease-1b
• MFRP gene
• posterior microphthalmos
• retinitis pigmentosa

Acknowledgment

We are grateful to Ms. Iman Al Harthi for technical assistance, and the patients and their family for their cooperation.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.