| | |  | | | | Record from Web of Science® | | | | | | |
| High-resolution mapping of the gene for cystinosis, using combined biochemical and linkage analysis |
|
|
| Author(s): Jean G, Fuchshuber A, Town MM, Gribouval O, Schneider JA, Broyer M, vantHoff W, Niaudet P, Antignac C |
| Source: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 58 Issue: 3 Pages: 535-543 Published: MAR 1996 |
| Times Cited: 22 References: 25 |
| Abstract: 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 Ist decade of life. Measurement of free cystine in purified polymorphonuclear leukocytes provides an accurate method for diagnosis and detection of heterozygous carriers. In order to localize the gene locus for cystinosis we performed linkage analysis in 18 cystinosis families. However, since 17 of these were simplex families, we decided to include the phenotypes of the 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. HOP NECKER ENFANTS MALAD, INSERM U423, F-75743 PARIS 15, FRANCE
2. HOP NECKER ENFANTS MALAD, DEPT PEDIAT NEPHROL, F-75743 PARIS 15, FRANCE
3. UNITED MED & DENT SCH, GUYS HOSP, DIV MED & MOLEC GENET, LONDON SE1 9RT, ENGLAND
4. INST CHILD HLTH, LONDON WC1N 1EH, ENGLAND
5. UNIV CALIF SAN DIEGO, DEPT PEDIAT, LA JOLLA, CA 92093 USA |
| Publisher: UNIV CHICAGO PRESS, 5720 S WOODLAWN AVE, CHICAGO, IL 60637 |
| Subject Category: Genetics & Heredity |
| IDS Number: TV564 |
| ISSN: 0002-9297 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |