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CRB1 – Nanophthalmos

Autosomal recessive nanophthalmos has been linked to a homozygous CRB1 variant in a single Turkish family presenting with severe hyperopia (>+8.0 D), reduced axial length (18–19 mm), retinal dystrophy, macular edema, and optic disc drusen. Genome-wide homozygosity mapping identified a 28-Mb region encompassing CRB1, and direct sequencing revealed a novel homozygous c.2498G>A (p.Gly833Asp) variant segregating with disease in two affected siblings (PMID:23077403).

Evidence Strength: Limited genetic evidence supports CRB1 involvement in nanophthalmos, based on a single family (two probands) with congruent clinical and genetic findings. No functional assays directly demonstrate a pathogenic role of CRB1 variants in ocular axial growth or refractive development.

Key Take-home: While CRB1 mutations are well-established in retinal dystrophies, this report expands its phenotypic spectrum to include syndromic nanophthalmos, warranting inclusion of CRB1 in genetic testing panels for nanophthalmos.

References

  • Molecular Vision • 2012 • A novel crumbs homolog 1 mutation in a family with retinitis pigmentosa, nanophthalmos, and optic disc drusen. PMID:23077403

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single family report with two probands and no additional segregation

Genetic Evidence

Limited

One homozygous CRB1 variant in two affected siblings; no replication

Functional Evidence

Limited

Lack of functional studies directly linking CRB1 variants to nanophthalmos phenotype