Molecular studies in Finnish patients with familial juvenile nephronophthisis exclude a founder effect and support a common mutation causing mechanism
| Autor: | Sirpa Ala-Mello, H Kääriäinen, E.-M. Sankila, Koskimies O, A. de la Chapelle |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Linkage disequilibrium medicine.medical_specialty Locus (genetics) Biology Genetic determinism Linkage Disequilibrium End stage renal disease 03 medical and health sciences 0302 clinical medicine Genetic linkage Internal medicine Genetics medicine Humans 030212 general & internal medicine Child Genetics (clinical) Finland 030304 developmental biology Polycystic Kidney Autosomal Recessive 0303 health sciences Haplotype medicine.disease Founder Effect 3. Good health Pedigree Endocrinology Haplotypes Chromosomes Human Pair 2 Mutation Nephritis Interstitial Female Gene Deletion Kidney disease Founder effect Research Article |
| Popis: | Familial juvenile nephronophthisis (NPH) is an autosomal recessive tubulointerstitial kidney disease associated with formation of medullary and corticomedullary cysts. It progresses to end stage renal failure and its biochemical defect is unknown. An NPH locus has been assigned to a 2 cM interval on chromosome 2q13 by linkage studies. Homozygous deletions of approximately 250 kb have been detected in 80% of familial cases and 65% of sporadic cases and a common mutation mechanism has been suggested. We examined 14 Finnish families for the presence or absence of a deletion. After detecting a deletion in 12 patients belonging to nine families, we studied a possible founder effect by haplotype analysis using markers D2S340, D2S1889, and D2S1893. No common ancestral disease associated haplotype was found suggesting no founder effect. Results of pairwise linkage analyses were suggestive of linkage in the nine families with a deletion (lod scores of 1.39-3.89 at a recombination fraction of 0). Negative lod scores were obtained in the five families without a deletion suggesting that the disease locus in these families lies elsewhere. The end stage renal disease occurred at a more advanced age in patients without a deletion compared to patients with a deletion, indicating a phenotypic difference between these two groups. |
| Databáze: | OpenAIRE |
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