Microphthalmia, Isolated, With Coloboma 6
A number sign (#) is used with this entry because of evidence that isolated microphthalmia with coloboma-6 (MCOPCB6) is caused by heterozygous mutation in the GDF3 gene (606522) on chromosome 12p13.
For a discussion of genetic heterogeneity of isolated colobomatous microphthalmia, see MCOPCB1 (300345).
Clinical FeaturesYe et al. (2010) reported a mother and daughter with colobomatous microphthalmia. The mother had mild bilateral iris colobomata, mild microphthalmia, normal optic discs and electroretinograms (ERGs), and visual acuity of 20/40 in each eye. The more severely affected daughter exhibited mixed horizontal and rotatory nystagmus, bilateral iris coloboma, severe colobomatous microphthalmia, bilateral foveal hypoplasia, abnormally small optic discs with reduced optic nerve diameters on MRI, visual acuity of 20/200, and abnormal ERGs with decreased a and b wave amplitudes.
Molecular GeneticsYe et al. (2010) screened DNA samples from 449 probands with isolated microphthalmia and/or coloboma and 23 probands with skeletal or oculoskeletal phenotypes for mutations in the GDF3 gene and identified heterozygous missense mutations in 3 probands with bilateral colobomatous microphthalmia: R266C (606522.0001) in 2 probands, and R274W (606522.0004) in 1 proband. One of the probands with R266C was a female patient whose affected mother also carried the R266C variant; in the more severely affected daughter, a missense mutation in the GDF6 gene (A199T; 601147.0007) was also detected.