Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very-early-onset disease

Terry Watnick, Bunyong Phakdeekitcharoen, Ann Johnson, Michael Gandolph, Mei Wang, Gary Briefel, Katherine W. Klinger, William J Kimberling, Patricia Gabow, Gregory G. Germino

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

It is known that several of the most severe complications of autosomal- dominant polycystic kidney disease, such as intracranial aneurysms, cluster in families. There have been no studies reported to date, however, that have attempted to correlate severely affected pedigrees with a particular genotype. Until recently, in fact, mutation detection for most of the PKD1 gene was virtually impossible because of the presence of several highly homologous loci also located on chromosome 16. In this report we describe a duster of 4 bp in exon 15 that are unique to PKD1. Forward and reverse PKD1- specific primers were designed in this location to amplify regions of the gene from exons 11-21 by use of long-range PCR. The two templates described were used to analyze 35 pedigrees selected for study because they included individuals with either intracranial aneurysms and/or very-early-onset disease. We identified eight novel truncating mutations, two missense mutations not found in a panel of controls, and several informative polymorphisms. Many of the polymorphisms were also present in the homologous loci, supporting the idea that they may serve as a reservoir for genetic variability in the PKD1 gene. Surprisingly, we found that three independently ascertained pedigrees had an identical 2-bp deletion in exon 15. This raises the possibility that particular genotypes may be associated with more-severe disease.

Original languageEnglish (US)
Pages (from-to)1561-1571
Number of pages11
JournalAmerican Journal of Human Genetics
Volume65
Issue number6
DOIs
StatePublished - Jan 1 1999

Fingerprint

Pedigree
Aneurysm
Exons
Intracranial Aneurysm
Mutation
Genotype
Genes
Autosomal Dominant Polycystic Kidney
Chromosomes, Human, Pair 16
Missense Mutation
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Watnick, T., Phakdeekitcharoen, B., Johnson, A., Gandolph, M., Wang, M., Briefel, G., ... Germino, G. G. (1999). Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very-early-onset disease. American Journal of Human Genetics, 65(6), 1561-1571. https://doi.org/10.1086/302657

Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very-early-onset disease. / Watnick, Terry; Phakdeekitcharoen, Bunyong; Johnson, Ann; Gandolph, Michael; Wang, Mei; Briefel, Gary; Klinger, Katherine W.; Kimberling, William J; Gabow, Patricia; Germino, Gregory G.

In: American Journal of Human Genetics, Vol. 65, No. 6, 01.01.1999, p. 1561-1571.

Research output: Contribution to journalArticle

Watnick, T, Phakdeekitcharoen, B, Johnson, A, Gandolph, M, Wang, M, Briefel, G, Klinger, KW, Kimberling, WJ, Gabow, P & Germino, GG 1999, 'Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very-early-onset disease', American Journal of Human Genetics, vol. 65, no. 6, pp. 1561-1571. https://doi.org/10.1086/302657
Watnick, Terry ; Phakdeekitcharoen, Bunyong ; Johnson, Ann ; Gandolph, Michael ; Wang, Mei ; Briefel, Gary ; Klinger, Katherine W. ; Kimberling, William J ; Gabow, Patricia ; Germino, Gregory G. / Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very-early-onset disease. In: American Journal of Human Genetics. 1999 ; Vol. 65, No. 6. pp. 1561-1571.
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