Retinal Dystrophy And Iris Coloboma With Or Without Congenital Cataract

A number sign (#) is used with this entry because of evidence that retinal dystrophy and iris coloboma with or without congenital cataract (RDICC) is caused by heterozygous mutation in the MIR204 gene (610942) on chromosome 9q21. One such family has been reported.

Clinical Features

Conte et al. (2015) reported a 5-generation British family segregating autosomal dominant nonsyndromic retinal dystrophy with iris coloboma. The proband was an 18-year-old male who was diagnosed with retinal dystrophy and bilateral iris coloboma in early childhood. Examination revealed reduced visual acuity (less than 20/100 bilaterally), significantly reduced color vision, and bilateral iris colobomata with iridolenticular adhesions. Funduscopy showed scattered mottling of the retinal pigment epithelium with retinal atrophy and attenuation of the retinal vasculature. Optical coherence tomography was consistent with severe photoreceptor loss. Electroretinography (ERG) revealed bilaterally extinguished responses to all conditions except a minimal residual light-adapted 30-Hz flicker response; the authors noted that an ERG 4 years earlier had shown less-attenuated light-adapted responses. The proband's 42-year-old mother was diagnosed in infancy with bilateral iris colobomata and progressive retinopathy. She underwent bilateral cataract surgery at 30 years of age, and was registered as blind. Examination showed hand movement vision in the right eye and no light perception in the left eye. Four additional family members were registered blind, including the proband's maternal grandmother and maternal great-uncle; all had bilateral iris coloboma and a slowly progressive retinal dystrophy leading to marked loss of vision by late childhood or early adult life. The maternal great-uncle also had congenital cataracts and underwent surgery at 7 years of age.

Mapping

In a 5-generation British family segregating autosomal dominant nonsyndromic retinal dystrophy with iris coloboma, Conte et al. (2015) performed linkage analysis and identified 4 regions over 5 Mb with lod scores between -2 and 1.81.

Molecular Genetics

In a 5-generation British family segregating autosomal dominant nonsyndromic retinal dystrophy and iris coloboma with or without congenital cataract, Conte et al. (2015) performed exome sequencing to detect possible causal variants within potential linked regions, and identified a point mutation in the MIR204 gene that was present in the 6 affected family members tested. The mutation was not found in 2 unaffected family members or in the Exome Variant Server or 1000 Genomes Project databases. Screening of the MIR204 gene in an additional 21 cases of retinal dystrophy with microphthalmia and coloboma, as well as in a cohort of 457 patients with isolated microphthalmia/anophthalmia and coloboma and 672 patients with autosomal dominant retinal degeneration, did not reveal any mutations.