Anirdia-like phenotype caused by 6p25 dosage aberrations.

Axenfeld-Rieger spectrum (ARS) includes the anterior segment abnormalities posterior embryotoxon, irido-corneal adhesions, corectopia, and other abnormalities of pupil size and shape. Glaucoma occurs in approximately 50% of affected children. It is often caused by mutations of FOXC1 or PITX2. Timing of expression and dosage of these transcription factors appear to be very critical in the development of the anterior segment. We report on one child with a deletion and another with a duplication involving 6p25, causing an anirdia-like phenotype. Classic anirdia is a pan-ophthalmic disorder caused by heterozygous mutations involving the paired homeobox gene PAX6 at 11p13. It is often associated with optic nerve hypoplasia, foveal hypoplasia, corneal pannus, nystagmus, and cataract. Microdeletion of 11p13 may be associated with life threatening Wilms tumor. Distinguishing these two syndromes has critical implications for prognosis and treatment. We demonstrate how chromosomal microarray can be instrumental in differentiating these phenotypes.

Autosomal-dominant Leber Congenital Amaurosis Caused by a Heterozygous CRX Mutation in a Father and Son.

BACKGROUND: Leber congenital amaurosis (LCA) is most often an autosomal recessive disorder. We report a father and son with autosomal dominant LCA due to a mutation in the CRX gene. MATERIALS AND METHODS: DNA screening using an allele specific assay of 90 of the most common LCA-causing variations in the coding sequences of AIPL1, CEP290, CRB1, CRX, GUCY2D, RDH12 and RPE65 was performed on the father. Automated DNA sequencing of his son examining exon 3 of the CRX gene was subsequently performed. RESULTS: Both father and son have a heterozygous single base pair deletion of an adenine at codon 153 in the coding sequence of the CRX gene resulting in a frameshift mutation. CONCLUSION: Mutations involving the CRX gene may demonstrate an autosomal dominant inheritance pattern for LCA.