Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus.

Waardenburg-Shah syndrome (Waardenburg syndrome type IV-WS4) is an auditory-pigmentary disorder that combines clinical features of pigmentary abnormalities of the skin, hair and irides, sensorineural hearing loss, and Hirschsprung disease (HSCR). Mutations in the endothelin-B receptor (EDNRB) gene on 13q22 have been found to cause this syndrome. Mutations in both alleles cause the full phenotype, while heterozygous mutations cause isolated HSCR or HSCR with minor pigmentary anomalies and/or sensorineural deafness. We investigated the status of the EDNRB gene, by FISH analysis, in three patients with de novo proximal 13q deletions detected at cytogenetic analysis and examined the clinical variability of WS4 among these patients. Chromosome 13q was screened with locus specific FISH probes and breakpoints were determined at 13q22.1q31.3 in Patients 1 and 3, and at 13q21.1q31.3 in Patient 2. An EDNRB specific FISH probe was deleted in all three patients. All patients had common facial features seen in proximal 13q deletion syndrome and mild mental retardation. However, findings related to WS4 were variable; Patient 1 had hypopigmentation of the irides and HSCR, Patient 2 had prominent bicolored irides and mild bilateral hearing loss, and Patient 3 had only mild unilateral hearing loss. These data contribute new insights into the pathogenesis of WS4.

Blood and lens lipid peroxidation and antioxidant status in normal individuals, senile and diabetic cataractous patients.

PURPOSE: Oxidative mechanisms are believed to play an important role in the pathogenesis of cataract, the most important cause of visual impairment at advanced age. To determine the body's antioxidant status as well as its lipid peroxidation levels, both blood and lens parameters were evaluated. METHODS: This study was performed on the blood samples and lenses obtained from 46 patients diagnosed as having cataract and 20 control subjects. The control group was composed of 10 women and 10 men who do not smoke. Control subjects without any lens opacity or vacuoles when observed with a slit lamp were recruited on the same exclusion criteria as far as disease and treatment were concerned. No antioxidant medicines were used. They were all healthy individuals without any systemic diseases. Superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GSSG-Red) activities in red blood cell (RBC) lysates as well as whole blood glutathione (GSH) and plasma thiobarbituric acid reactive substances (TBARS), the indicator of lipid peroxidation concentrations, were determined quantitatively both in the blood samples and the lenses of the patients with senile and diabetic cataracts. RESULTS: Whole blood GSH values, and erythrocyte SOD activities were significantly lower in the cataractous patients than those in the control group. The values in the diabetic cataractous group were also less than those in the senile cataractous group. Significantly decreased erythrocyte GSSG-Red and G6PD activities were detected in the diabetic cataractous group. Plasma TBARS values were higher both in the senile and diabetic groups when compared to those in the control group. Significantly decreased values were observed for GSSG-Red activities and TBARS values in the lenses of the senile cataractous patients in comparison with those in the diabetic cataractous patients. The lens GSH values were found to be higher in the senile cataractous group than the values obtained in the diabetic cataractous group. CONCLUSIONS: A strong correlation was found between lens GSH and lens TBARS concentrations in the diabetic group. This emphasized the vital role of GSH as an antioxidant in the lens over the other antioxidant parameters, e.g., enzymes, and the oxidative stress is at the highest level in lens.