ABSTRACT
Glaucoma is an inherited complex and heterogeneous disease, and one of the most prevalent causes of definitive blindness in the world. Recent reports have indicated that heterozygous mutations of the CYTOCHOROME P4501B1 (CYP1B1) gene are present in 4-10% of patients with primary open-angle glaucoma (POAG). To further evaluate the role of CYP1B1 mutations in POAG we extended our previous association study and carried out a functional analysis of the mutations identified by polymerase chain reaction (PCR) DNA sequencing of the three exons of the gene in a total of 245 unrelated Spanish patients and 326 control subjects. Eight of nine different mutations identified in these patients were cloned and functionally assessed by measuring ethoxyresorufin O-deethylation activity and CYP1B1 stability in transiently transfected HEK-293T cells. All these mutants showed reduced catalytic activity, ranging from 20% to 60% of wild-type and/or decreased protein stability and, therefore, they were classified as hypomorphic alleles. No null alleles were identified in these patients. We found heterozygous hypomorphic CYP1B1 mutations in 17 (6.7%) patients and in seven controls (2.1%) showing that these mutations are associated with an increased risk of POAG (p = 0.005; odds ratio = 3.2; 95% confidence interval = 1.30-9.19). Our data suggest that hypomorphic CYP1B1 mutations are, to date, the main known genetic risk factor in POAG.
Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Glaucoma, Open-Angle/genetics , Aged , Aged, 80 and over , Amino Acid Sequence , Cell Line , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1B1 , Female , Genetic Predisposition to Disease , Genetic Testing , Heterozygote , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation , SpainABSTRACT
CASE REPORT: A 43-year-old woman referred for a hyperemic node in the inferior conjunctival fornix. No improvement was observed after 10 days of antibiotic and anti-inflammatory topical treatment, so biopsy-extirpation was performed. Histopathological and immunohistochemical findings suggested the diagnosis of Langerhans cell histiocytosis (LCH). No findings of extraocular manifestations were shown after an intensive clinical and analytical investigation. DISCUSSION: LCH is a disease with different organ manifestations whose diagnosis depends on histological findings. We present a patient with isolated conjunctival affectation, which to our knowledge is the third case published in the literature.
Subject(s)
Conjunctival Diseases/pathology , Histiocytosis, Langerhans-Cell/pathology , Adult , Antigens, CD1/analysis , Biomarkers , Conjunctival Diseases/diagnosis , Conjunctival Diseases/surgery , Female , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/surgery , Humans , Hyperemia/etiology , S100 Proteins/analysisABSTRACT
CASE REPORT: Miller Fisher Syndrome (MFS) is the most frequent variant of the Guillain-Barré Syndrome. It is characterised by the classic triad of ophthalmoplegia, ataxia and areflexia. We present a case of a patient who developed these clinical findings 5 days after flu vaccination. DISCUSSION: Miller Fisher Syndrome is an unusual condition seen in ophthalmologic clinical practice. Although respiratory and digestive infections have been reported as antecedent infectious agents in MFS, it has not previously been described in relation to the flu vaccine.