Tuesday 7 February 2012
Definition: X-linked megalocornea (MGC1) is an ocular anterior segment disorder characterized by an increased cornea diameter and deep anterior chamber evident at birth and later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts.
copy-number variation, frameshift, missense, splice-site and nonsense mutations in the Chordin-like 1 gene (CHRDL1) on Xq23 as the cause of the condition in seven MGC1 families.
- CHRDL1 encodes ventroptin, a bone morphogenic protein antagonist with a proposed role in specification of topographic retinotectal projections.
- Electrophysiological evaluation revealed mild generalized cone system dysfunction and, in one patient, an interhemispheric asymmetry in visual evoked potentials.
- CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina.
- CHRDL1 is differentially expressed in the human fetal brain, and there is high expression in cerebellum and neocortex.
- MGC1 patients have a superior cognitive ability despite a striking focal loss of myelination of white matter.
- There is an unexpected requirement for ventroptin during anterior segment development and the consequences of a lack of function in the retina and brain.
X-Linked Megalocornea Caused by Mutations in CHRDL1 Identifies an Essential Role for Ventroptin in Anterior Segment Development. Webb TR, Matarin M, Gardner JC, Kelberman D, Hassan H, Ang W, Michaelides M, Ruddle JB, Pennell CE, Yazar S, Khor CC, Aung T, Yogarajah M, Robson AG, Holder GE, Cheetham ME, Traboulsi EI, Moore AT, Sowden JC, Sisodiya SM, Mackey DA, Tuft SJ, Hardcastle AJ. Am J Hum Genet. 2012 Jan 24. PMID: 22284829