Two novel missense substitutions in the VSX1 gene: clinical and genetic analysis of families with Keratoconus from India

BACKGROUND: Visual system homeobox gene (VSX1) plays a major role in the early development of craniofacial and ocular tissues including cone opsin gene in the human retina. To date, few disease-causing mutations of VSX1 have been linked to familial and sporadic keratoconus (KC) in humans. In this study, we describe the clinical features and screening for VSX1 gene in families with KC from India. METHODS: Clinical data and genomic DNA were collected from patients with clinically diagnosed KC and their family members. The study was conducted on 20 subjects of eight families from India. The coding exons of VSX1 gene were amplified using PCR and amplicons were analyzed by direct sequencing. Predictive effect of the mutations was performed using Polyphen-2, SIFT and mutation assessor algorithms. Additionally, haplotypes of VSX1 gene were constructed for affected and unaffected individuals using SNPs. RESULTS: In the coding region of VSX1, one novel missense heterozygous change (p.Leu268His) was identified in five KC patients from two unrelated families. Another family of three members had a novel heterozygous change (p.Ser251Thr). These variants co-segregated with the disease phenotype in all affected individuals but not in the unaffected family members and 105 normal controls. In silico analysis suggested that p.Leu268His could have a deleterious effect on the protein coded by VSX1, while p.Ser251Thr has a neutral effect on the functional properties of VSX1. Haplotype examination revealed common SNPs around the missense change (p.Leu268His) in two unrelated KC families. CONCLUSIONS: In this study, we add p.Leu268His, a novel missense variation in the coding region of VSX1 to the existing repertoire of VSX1 coding variations observed in Indian patients with the characteristic phenotype of KC. The variant p.Ser251Thr might be a benign polymorphism, but further biophysical studies are necessary to evaluate its molecular mechanism. The shared haplotype by two families with the same variant suggests the possibility of a founder effect, which requires further elucidation. We suggest that p.Leu268His might be involved in the pathogenesis of KC, which may help in the genetic counselling of patients and their family

Correlation of clinical and neuroradiological findings in down-gaze palsy

Background: Isolated down-gaze palsy is the least common pathology of vertical gaze. Patients with low-gaze palsy may consult an ophthalmologist with difficulty in reading and this may be the only ocular finding of a central nervous system lesion. Methods: A 43-year-old man with isolated down-gaze palsy was examined. The medical history of the patient revealed that he had had myocardial infarction. Result: Magnetic resonance imaging disclosed an ischemic area at the right thalamus. Conclusion: Down-gaze palsy may be an important sign for the diagnosis of thalamic infarctions due to embolic syndrome

strains

The emergence of phenotypic resistance to ciprofloxacin and levofloxacin in methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) strains was studied. Twenty MRSA and 77 methicillin-sensitive S.aureus (MSSA) strains susceptible to both quinolones were investigated for resistance after single step or serial passages. No growth of 20 MRSA strains was observed at 4 x MIC of levofloxacin after 48 h incubation, but 4 of 77 (5%) MSSA strains grew at the same concentration. At 4 x MIC concentration of ciprofloxacin, 10 MSSA (13%) and five MRSA (25%) strains were grown. In the serial passages of MRSA strains, resistance to ciprofloxacin was 75 and 5% for levofloxacin by the third passage. In the seventh passage this resistance was 100 and 15%, respectively. In MSSA strains, resistance to ciprofloxacin was 75 and 19% to levofloxacin at the third passage and at the seventh passage, 100 and 61%, respectively. Emergence of ciprofloxacin resistance was more common and developed more rapidly than resistance to levofloxacin in both MRSA and MSSA strains. (C) 2003 Elsevier Science B.V. and the International Society of Chemotherapy. All rights reserved

External ocular infections due to methicillin-resistant Staphylococcus aureus (MRSA)

Purpose: To determine the prevalence and clinical characteristics of external ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in an ophthalmic hospital in the UK. Methods: A retrospective analysis of the case notes of patients who had culture proven external ocular Staphylococcal infections during a 44-month period was undertaken. Results: There were a total of 548 external eye infections caused by Staphylococcus aureus. Of these, 17 (3%) were MRSA positive. The most common presentation was conjunctivitis seen in six patients. All MRSA isolates were sensitive to chloramphenicol. Ofloxacin resistance was observed in all isolates from patients over the age of 50 years. All patients had an underlying history of either an ocular surface disease, malignancy, or a debilitating medical illness. Conclusions: MRSA is as yet an infrequent cause of external ocular infections. Patients typically have underlying ocular risk factors and/or are medically debilitated. Different strains infect young and old age groups with characteristic antimicrobial sensitivity. This study highlights the need for more work to establish the role of MRSA commensals and ocular infections. © 2005 Nature Publishing Group All rights reserved