Microphthalmia, Isolated, With Coloboma 3

A number sign (#) is used with this entry because isolated colobomatous microphthalmia-3 (MCOPCB3) is caused by homozygous mutation in the CHX10 gene (142993) on chromosome 14q24.

For a discussion of genetic heterogeneity of isolated colobomatous microphthalmia, see MCOPCB1 (300345).

Clinical Features

Zlotogora et al. (1994) studied isolated colobomatous microphthalmia in multiple relatives of 5 consanguineous families. Microphthalmia was unilateral or bilateral; additional eye findings included microcornea and colobomas of the iris, choroid, optic discs, and/or optic nerve. The intelligence of all the affected members was normal. Three of the families were in an Iranian Jewish community where Zlotogora et al. (1994) suggested that the putative gene may have an unusually high frequency.

Microphthalmia, Cataracts, and Iris Abnormalities

Percin et al. (2000) examined a 9-month-old male infant and his 49-year-old paternal great-uncle from a consanguineous 4-generation Turkish family; both had bilateral microphthalmia, congenital cataracts, and bilateral inferior iris colobomas, with no nonocular abnormalities. A third individual, a 2-month-old male infant from a consanguineous Arab family, had bilateral microphthalmia with no pupillary aperture, a funnel-shaped retinal detachment inserted into the optic disc on the right, and a lesion compatible with a dislocated lens with surrounding membrane formation or localized retinal detachment on the left. He also had bilateral undescended testes.

Mapping

In a 4-generation Turkish family with bilateral microphthalmia, cataract, and coloboma of the iris, Percin et al. (2000) excluded linkage to the MCOP1 locus (251600) at 14q32. Cosegregation of microphthalmia was observed only with DNA markers flanking CHX10 on 14q24.3; a maximum lod score of 2.81 was obtained for the markers D14S77, the CHX10 CA repeat, and D14S1047.

Molecular Genetics

In 2 affected individuals from a 4-generation consanguineous Turkish family with microphthalmia, cataract, and coloboma, and in the proband from a consanguineous Arab family with microphthalmia and absent pupils, Percin et al. (2000) identified homozygosity for 2 missense mutations in the CHX10 gene (142993.0001 and 142993.0002, respectively).

In affected members of a consanguineous Jewish Syrian (Halabi) family with microphthalmia/clinical anophthalmia and colobomas of the iris, Bar-Yosef et al. (2004) identified homozygosity for a splice site mutation in the CHX10 gene (142993.0005).