Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea

• Published in: Human molecular genetics Vol. 13; no. 3; pp. 315 - 322
• Main Authors: Voronina, Vera A., Kozhemyakina, Elena A., O'Kernick, Christina M., Kahn, Natan D., Wenger, Sharon L., Linberg, John V., Schneider, Adele S., Mathers, Peter H.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2004; Oxford Publishing Limited (England)
• Subjects: Anophthalmos - genetics; Biological and medical sciences; Child, Preschool; Classical genetics, quantitative genetics, hybrids; Codon, Nonsense; Cornea - abnormalities; Eye Proteins - genetics; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Homeodomain Proteins - genetics; Human; Humans; Infant, Newborn; Male; Malformations of the eye; Medical sciences; Molecular and cellular biology; Mutation, Missense; Ophthalmology; Orbit - abnormalities; Orbit - diagnostic imaging; Pedigree; Radiography; RAX gene; Transcription Factors - genetics; Human; Eye disease; Gene; Malformation; Genetics; Patient; Sclerocornea; Mutation; Congenital disease; Anophthalmos
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddh025

Anophthalmia and microphthalmia are among the most common ocular birth defects and a significant cause of congenital blindness. The etiology of anophthalmia and microphthalmia is diverse, with multiple genetic mutations associated with each of these conditions, along with potential environmental causes. Based on findings that mutations in the Rx/Rax homeobox genes in mice and fish lead to defects in retinal development and result in animal models of anophthalmia, we screened 75 individuals with anophthalmia and/or microphthalmia for mutations in the human RAX gene. We identified a single proband from this population who is a compound heterozygote for mutations in the RAX gene. This individual carries a truncated allele (Q147X) and a missense mutation (R192Q), both within the DNA-binding homeodomain of the RAX protein, and we have characterized the biochemical properties of these mutations in vitro. Parents and grandparents of the proband were found to be carriers without visible ocular defects, consistent with an autosomal recessive inheritance pattern. This is the first report of genetic mutations in the human RAX gene.