A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1)

Belén Peral, Albert C M Ong, José L. San Millán, Vicki Gamble, Lesley Rees, Peter C Harris

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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common single gene disorder resulting in renal failure. It is generally an adult onset disease, but rarely, cases of severe childhood polycystic disease arise in ADPKD families. The clear clinical anticipation in these pedigrees has led to the suggestion that the mutation may be an unstable trinucleotide repeat. We have now identified a nonsense mutation, Tyr3818Stop, in one such family (P117) within the major ADPKD gene, polycystic kidney disease 1 (PKD1). The mutation is shown to be a de novo change in the father, and of grandpaternal origin, PKD1 manifests as typical adult onset disease in the father, but is seen as severe disease, detected as enlarged polycystic kidneys in utero, in one of a pair of dizygotic twins; the other twin has the mutation but no evidence of cysts, consistent with an adult onset disease course. The finding of the same stable mutation associated with very different disease severity in this family indicates that phenotypic variation in PKD1 is not due to a dynamic mutation. It seems most likely that a small number of modifying factors may radically affect the course of disease in PKD1; identification of such factors will have important prognostic implications in this disorder.

Original languageEnglish (US)
Pages (from-to)539-542
Number of pages4
JournalHuman Molecular Genetics
Volume5
Issue number4
DOIs
StatePublished - Apr 1996
Externally publishedYes

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Polycystic Kidney Diseases
Nonsense Codon
Autosomal Dominant Polycystic Kidney
Mutation
Fathers
Trinucleotide Repeats
Dizygotic Twins
Pedigree
Genes
Renal Insufficiency
Cysts

ASJC Scopus subject areas

  • Genetics

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A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1). / Peral, Belén; Ong, Albert C M; San Millán, José L.; Gamble, Vicki; Rees, Lesley; Harris, Peter C.

In: Human Molecular Genetics, Vol. 5, No. 4, 04.1996, p. 539-542.

Research output: Contribution to journalArticle

Peral, Belén ; Ong, Albert C M ; San Millán, José L. ; Gamble, Vicki ; Rees, Lesley ; Harris, Peter C. / A stable, nonsense mutation associated with a case of infantile onset polycystic kidney disease 1 (PKD1). In: Human Molecular Genetics. 1996 ; Vol. 5, No. 4. pp. 539-542.
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