COL4A3Founder Mutations in Greek-Cypriot Families with Thin Basement Membrane Nephropathy and Focal Segmental Glomerulosclerosis Dating from Around 18th Century
| Autor: | Voskarides, Konstantinos, Patsias, Charalambos, Pierides, Alkis M., Constantinou-Deltas, Constantinos D. |
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| Přispěvatelé: | Constantinou-Deltas, Constantinos D. [0000-0001-5549-9169] |
| Rok vydání: | 2008 |
| Předmět: |
haplotype
Linkage disequilibrium family kidney disease Nephritis Hereditary History 18th Century Autoantigens geography Linkage Disequilibrium ethnic group Type IV collagen Focal segmental glomerulosclerosis Glomerular Basement Membrane gene mutation Genetics (clinical) Genetics education.field_of_study Glomerulosclerosis Focal Segmental thin basement membrane nephropathy article Founder Effect Pedigree female medicine.anatomical_structure col4a3 gene Mutation (genetic algorithm) Kidney Diseases focal glomerulosclerosis Collagen Type IV European Continental Ancestry Group Population chromosome number Biology White People male medicine Humans Family controlled study human gene education Basement membrane Haplotype medicine.disease gene linkage disequilibrium Haplotypes Genetic marker Cyprus Mutation |
| Zdroj: | Genetic testing Genet.Test. |
| ISSN: | 1557-7473 1090-6576 |
| DOI: | 10.1089/gte.2007.0110 |
| Popis: | Mutations in the COL4A3/COL4A4 genes of type IV collagen account for about 40% of cases of thin basement membrane nephropathy, a condition that is estimated to affect 1% or more of the general population. We recently described 10 Cypriot families with familial hematuria and thin basement membrane nephropathy in the presence of focal segmental glomerulosclerosis, with founder mutations on COL4A3 gene. Seven of the families carried mutation G1334E on haplotype K, and another three carried mutation G871C on haplotype Ky. In this report we performed extension of the haplotypes with additional polymorphic markers, 12 for haplotype K and 22 for haplotype Ky, to estimate the linkage disequilibrium value between the mutation and flanking noncommon markers. Haplotype Ky extended to 13.71 Mb, but we did not attempt further analysis owing to the small number of chromosomes. Haplotype K extended to 3.83 Mb, thereby suggesting that it was a much older event compared to mutation G871C. Mutation G1334E was calculated to be about 5-10 generations old with a possible origin between 1693 and 1818 AD, during the Ottoman ruling of the island. Both mutations are clustered in specific geographic regions with apparently formerly isolated populations, although mutation G1334E has been detected elsewhere on the island. The identification of founder mutations in large families with microscopic hematuria greatly facilitates presymptomatic diagnosis and provides useful information on the history of the population, while it may also assist in association studies in search for disease modifier genes. © Copyright, Mary Ann Liebert, Inc. 2008. 12 273 278 Cited By :10 |
| Databáze: | OpenAIRE |
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