Microphthalmia, Isolated, With Coloboma 1

Description

Ocular coloboma is a developmental defect of the eye resulting from abnormal or incomplete fusion of the optic fissure. The defect can be unilateral or bilateral and can involve the cornea, iris, ciliary body, lens, choroid, retina, and/or optic nerves. Clinically, coloboma is often associated with microphthalmia or clinical anophthalmia and can occur as part of complex malformation syndromes (summary by Wang et al., 2012).

Genetic Heterogeneity of Isolated Microphthalmia With Coloboma

Isolated colobomatous microphthalmia-1 (MCOPCB1) has been mapped to the X chromosome. MCOPCB2 (605738) has been mapped to chromosome 15q12-q15. MCOPCB3 (610092) is caused by mutation in the CHX10 gene (142993) on chromosome 14q24. MCOPCB5 (611638) is caused by mutation in the SHH gene (600725) on chromosome 7q36. MCOPCB6 (613703) is caused by mutation in the GDF3 gene (606522) on chromosome 12p13.1. MCOPCB7 (614497) is caused by mutation in the ABCB6 gene (605452) on chromosome 2q36. MCOPCB8 (see 601186) is caused by mutation in the STRA6 gene (601745) on chromosome 15q24. MCOPCB9 (615145) is caused by mutation in the TENM3 gene (610083) on chromosome 4q35. See 251505 for a discussion of MCOPCB4.

Clinical Features

Lehman et al. (2001) reported a large 3-generation Mexican American family with apparent X-linked recessive transmission of isolated colobomatous microphthalmia. The affected family members were 9 males and 1 female in the third generation and their maternal grandfather. Their features included microphthalmia, ocular coloboma, microcornea with narrowed palpebral fissures, and elevated intraocular pressure.

Mapping

By genotyping and linkage analysis on a portion of the Mexican American family with isolated colobomatous microphthalmia, Lehman et al. (2001) obtained a maximum 2-point lod score of 2.71 with microsatellite markers DXS1058, DXS6810, DXS1199, and DXS7132, placing the disease locus on the proximal short arm or proximal long arm of the X chromosome. A single affected heterozygous female was observed in this family. She had a normal karyotype and normal, random X inactivation in her lymphocyte DNA. However, skewed X inactivation in the cell lineages from which the eye was derived could not be ruled out.