Homozygous FOXE3 mutations cause non-syndromic, bilateral, total sclerocornea, aphakia, microphthalmia and optic disc coloboma.

PURPOSE: To investigate the genetic basis of recessively-inherited congenital, non syndromic, bilateral, total sclerocornea in two consanguineous pedigrees, one from the Punjab province of Pakistan and the other from the Tlaxcala province of Mexico. METHODS: Ophthalmic examinations were conducted on each family member to confirm their diagnosis and magnetic resonance imaging (MRI) or ultrasonography of the eyes was performed on some family members. Genomic DNA was analyzed by homozygosity mapping using the Affymetrix 6.0 SNP array and linkage was confirmed with polymorphic microsatellite markers. Candidate genes were sequenced. RESULTS: A diagnosis of autosomal recessive sclerocornea was established for 7 members of the Pakistani and 8 members of the Mexican pedigrees. In the Pakistani family we established linkage to a region on chromosome 1p that contained Forkhead Box E3 (FOXE3), a strong candidate gene since FOXE3 mutations had previously been associated with various anterior segment abnormalities. Sequencing FOXE3 identified the previously reported nonsense mutation, c.720C>A, p.C240X, in the Pakistani pedigree and a novel missense mutation which disrupts an evolutionarily conserved residue in the forkhead domain, c.292T>C, p.Y98H, in the Mexican pedigree. Individuals with heterozygous mutations had no ocular abnormalities. MRI or ultrasonography confirmed that the patients with sclerocornea were also aphakic, had microphthalmia and some had optic disc coloboma. CONCLUSIONS: This is the fourth report detailing homozygous FOXE3 mutations causing anterior segment abnormalities in human patients. Previous papers have emphasized aphakia and microphthalmia as the primary phenotype, but we find that the initial diagnosis - and perhaps the only one possible in a rural setting - is one of non-syndromic, bilateral, total sclerocornea. Dominantly inherited anterior segment defects have also been noted in association with heterozygous FOXE3 mutations. However the absence of any abnormalities in the FOXE3 heterozygotes described suggests that genetic background and environmental factors plays a role in the penetrance of the mutant allele.

Nurse specialist treatment of eye emergencies: five year follow up study of quality and effectiveness.

The role of specialist nurses in triage, diagnosis and management of emergency eye conditions is well established, and encouraging reports of the safety and effectiveness of such services have been published. Specialist nurses in an emergency eye clinic in the UK seeing >7000 patients per year had been found at initial evaluation to treat 22% of the 1976 patients seen over a three month period without referring on to an ophthalmologist. A repeat of this evaluation five years later found this proportion had dropped to 17% (chi(2) = 16.7, p<0.01). In addition, the initial evaluation had found no incident of any patient having been treated and discharged by the specialist nurses returning to the department due to incorrect diagnosis or mismanagement. By contrast, from the sample 5 years later, 3 patients were identified who returned to the department due to possible misdiagnosis or sub-optimal management. We suggest that provision must be made for continuing professional development of nurses in this type of extended role, and the commitment to ongoing education should be backed up by a system of monitoring and critical incident reporting to facilitate skill maintenance and the life long learning process for specialist nurses.