Renal cystic disease in tuberous sclerosis: Role of the polycystic kidney disease 1 gene

Julian R. Sampson, Magitha M. Maheshwar, Richard Aspinwall, Peter Thompson, Jeremy P. Cheadle, David Ravine, Sushmita Roy, Eric Haan, Jay Bernstein, Peter C Harris

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

Tuberous sclerosis is an autosomal dominant trait characterized by the development of hamartomatous growths in many organs. Renal cysts are also a frequent manifestation. Major genes for tuberous sclerosis and autosomal dominant polycystic kidney disease, TSC2 and PKD1, respectively, lie adjacent to each other at chromosome 16p13.3, suggesting a role for PKD1 in the etiology of renal cystic disease in tuberous sclerosis. We studied 27 unrelated patients with tuberous sterosis and renal cystic disease. Clinical histories and radiographic features were reviewed, and renal function was assessed. We sought mutations at the TSC2 and PKD1 loci, using pulsed field- and conventional-gel electrophoresis and FISH. Twenty-two patients had Contiguous deletions of TSC2 and PKD1. In 17 patients with constitutional deletions, cystic disease was severe, with early renal insufficiency. One patient with deletion of TSC2 and of only the 3' UTR of PKD1 had few cysts. Four patients were somatic mosaics; the severity of their cystic disease varied considerably. Mosaicism and mild cystic disease also were demonstrated in parents of 3 of the constitutionally deleted patients. Five patients without contiguous deletions had relatively mild cystic disease, 3 of whom had gross rearrangements of TSC2 and 2 in whom no mutation was identified. Significant renal cystic disease in tuberous sterosis usually reflects mutational involvement of the PKD1 gene, and mosaicism for large deletions of TSC2 and PKD1 is a frequent phenomenon.

Original languageEnglish (US)
Pages (from-to)843-851
Number of pages9
JournalAmerican Journal of Human Genetics
Volume61
Issue number4
StatePublished - Oct 1997
Externally publishedYes

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Cystic Kidney Diseases
Polycystic Kidney Diseases
Tuberous Sclerosis
Genes
Mosaicism
Cysts
Kidney
Autosomal Dominant Polycystic Kidney
Mutation
Pulsed Field Gel Electrophoresis
3' Untranslated Regions
Growth and Development
Renal Insufficiency
Chromosomes
Parents

ASJC Scopus subject areas

  • Genetics

Cite this

Sampson, J. R., Maheshwar, M. M., Aspinwall, R., Thompson, P., Cheadle, J. P., Ravine, D., ... Harris, P. C. (1997). Renal cystic disease in tuberous sclerosis: Role of the polycystic kidney disease 1 gene. American Journal of Human Genetics, 61(4), 843-851.

Renal cystic disease in tuberous sclerosis : Role of the polycystic kidney disease 1 gene. / Sampson, Julian R.; Maheshwar, Magitha M.; Aspinwall, Richard; Thompson, Peter; Cheadle, Jeremy P.; Ravine, David; Roy, Sushmita; Haan, Eric; Bernstein, Jay; Harris, Peter C.

In: American Journal of Human Genetics, Vol. 61, No. 4, 10.1997, p. 843-851.

Research output: Contribution to journalArticle

Sampson, JR, Maheshwar, MM, Aspinwall, R, Thompson, P, Cheadle, JP, Ravine, D, Roy, S, Haan, E, Bernstein, J & Harris, PC 1997, 'Renal cystic disease in tuberous sclerosis: Role of the polycystic kidney disease 1 gene', American Journal of Human Genetics, vol. 61, no. 4, pp. 843-851.
Sampson JR, Maheshwar MM, Aspinwall R, Thompson P, Cheadle JP, Ravine D et al. Renal cystic disease in tuberous sclerosis: Role of the polycystic kidney disease 1 gene. American Journal of Human Genetics. 1997 Oct;61(4):843-851.
Sampson, Julian R. ; Maheshwar, Magitha M. ; Aspinwall, Richard ; Thompson, Peter ; Cheadle, Jeremy P. ; Ravine, David ; Roy, Sushmita ; Haan, Eric ; Bernstein, Jay ; Harris, Peter C. / Renal cystic disease in tuberous sclerosis : Role of the polycystic kidney disease 1 gene. In: American Journal of Human Genetics. 1997 ; Vol. 61, No. 4. pp. 843-851.
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