High-resolution mapping of the gene for cystinosis, using combined biochemical and linkage analysis
- Hopital Nekcer-Enfants Malades, Paris (France); and others
Infantile nephropathic cystinosis is an autosomal recessive disorder characterized biochemically by an abnormally high intracellular content of free cystine in different organs and tissues due to a transport defect of cystine through the lysosomal membrane. Affected children present with the Fanconi syndrome and usually develop progressive renal failure within the 1st decade of life. Measurement of free cystine in purified polymorphonuclear leukocytes provides an accurate method for diagnosis and detection of heterozygous carriers previously determined by their leukocyte cystine content in the linkage analysis. This approach allowed us to obtain highly significant results, confirming the localization of the cystinosis gene locus recently mapped to the short arm of chromosome 17 by the Cystinosis Collaborative Research Group. Crucial recombination events allowed us to refine the interval of the cystinosis gene to a genetic distance of 1 cM. No evidence of genetic heterogeneity was found. Our results demonstrate that the use of the previously determined phenotypes of heterozygous carriers in linkage analysis provides a reliable method for the investigation of simplex families in autosomal recessive traits. 25 refs., 4 figs., 1 tab.
- OSTI ID:
- 381281
- Journal Information:
- American Journal of Human Genetics, Vol. 58, Issue 3; Other Information: PBD: Mar 1996
- Country of Publication:
- United States
- Language:
- English
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