Anti-CTSH monoclonal antibody, clone FQS8713

PURPOSE. Keratoconus and cataract are common causes of visual morbidity. Both conditions show genetic predisposition. The purpose of this study was to map the disease locus in a large three-generation family affected by combined early-onset autosomal dominant anterior polar cataract and clinically severe keratoconus. Uniquely, in this family both disorders were present and fully penetrant in those affected. METHODS. Thirty members of the family were examined clinically on two occasions, at an interval of 5 years, to establish their phenotypes and determine the progression of the disease. Genomic DNA was extracted from blood samples of 16 affected and 14 unaffected individuals, and typed with more than 350 highly polymorphic microsatellite loci in a genome-wide linkage screen. Markers were amplified by PCR with fluorescently labeled primers and sized with an automated DNA analyser before calculation of lod scores. After linkage was established, several positional candidate genes were assessed by PCR-based DNA sequencing. RESULTS. The locus for keratoconus with cataract was mapped to a 6.5-Mb region of the long arm of chromosome 15, at 22.33-24.2 between CYP11A and D15S211. The positional and functional candidate genes CTSH, CRABP1, IREB2, and RAS-GRF1 were excluded as the cause of keratoconus with cataract in this family. CONCLUSIONS. This is the first report of a family with autosomal dominant inheritance of keratoconus in association with cataract. The causative gene maps to the long arm of chromosome 15 but has not yet been identified.

The objective of the work was to verify the validity of parallel determination of total thyroxine (tT(4)) and thyrotropin (cTSH) concentrations in the diagnosis of primary hypothyroidism in the dog. The concentrations of total thyroxine and thyrotropin were determined by chemiluminiscence immunoassay in the serum of a total of 117 dogs: 40 negative controls, 66 dogs with euthyroid sick syndrome and I I patients with primary hypothyroidism. The average tT4 concentration in the group of healthy dogs was 25.8 +/- 5.48 nmol/l and the average cTSH concentration was 0.17 +/- 0.13 ng/ml. In the group of patients with primary hypothyroidism the tT(4) concentrations were significantly decreased in 10 out of 11 cases (10.12 +/- 2.01 nmol/l), while the cTSH concentrations were significantly increased (2.9 +/- 2.04 ng/ml). In one patient with primary hypothyroidism, only the tT(4) concentration was decreased to 9.0 nmol/l, but the cTSH concentration was found to be within the reference range (0.04 ng/ml). The average tT(4) concentration in the group of patients with euthyroid sick syndrome was 11.7 +/- 3.16 nmol/l, while the average cTSH concentration in the same group of patients was 0.14 +/- 0.12 ng/ml. The concentrations of tie two hormones mentioned above were compared between the different groups using the non-parametric Mann-Whitney test. The concentration of tT(4) was significantly higher (p < 0.01) in the group of healthy dogs compared to the dogs with primary hypothyroidism and the dogs with euthyroid sick syndrome. The concentration of cTSH was significantly higher(p < 0.01) in the dogs with primary hypothyroidism compared to the healthy dogs and the dogs with euthyroid sick syndrome. The results of this work show that parallel determination of tT(4) and cTSH represents a highly sensitive and specific method which is suitable for differentiating between primary hypothyroidism and other diseases that significantly reduce tT4 concentrations.