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. 1999 Jun;64(6):1655–1660. doi: 10.1086/302414

Identification of a new locus for medullary cystic disease, on chromosome 16p12.

F Scolari 1, D Puzzer 1, A Amoroso 1, G Caridi 1, G M Ghiggeri 1, R Maiorca 1, P Aridon 1, M De Fusco 1, A Ballabio 1, G Casari 1
PMCID: PMC1377908  PMID: 10330352

Abstract

Autosomal dominant medullary cystic disease (ADMCKD) is an interstitial nephropathy that has morphologic and clinical features similar to autosomal recessive nephronophthisis. The typical renal dysfunction associated with ADMCKD results mainly from a defect in urinary concentration ability, although results of urinalysis are normal. Recently, a locus on chromosome 1 was associated with ADMCKD, in DNA from two large Cypriot families, and genetic heterogeneity was inferred. We describe the genomewide linkage mapping of a new locus for medullary cystic disease, ADMCKD2, on chromosome 16p12 in a four-generation Italian pedigree. The family with ADMCKD2 fulfills the typical diagnostic criteria of ADMCKD, complicated by hyperuricemia and gouty arthritis. Marker D16S3036 shows a maximum two-point LOD score of 3.68, and the defined critical region spans 10.5 cM, between D16S500 and SCNN1B1-2. Candidate genes included in the critical region are discussed.

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Selected References

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  1. Allen F., Tisher C. C. Morphology of the ascending thick limb of Henle. Kidney Int. 1976 Jan;9(1):8–22. doi: 10.1038/ki.1976.2. [DOI] [PubMed] [Google Scholar]
  2. Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L., Riggs M., Wigler M., Ferguson K. A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs. Mol Cell Biol. 1993 Oct;13(10):6558–6571. doi: 10.1128/mcb.13.10.6558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Christodoulou K., Tsingis M., Stavrou C., Eleftheriou A., Papapavlou P., Patsalis P. C., Ioannou P., Pierides A., Constantinou Deltas C. Chromosome 1 localization of a gene for autosomal dominant medullary cystic kidney disease. Hum Mol Genet. 1998 May;7(5):905–911. doi: 10.1093/hmg/7.5.905. [DOI] [PubMed] [Google Scholar]
  4. Cole S. P., Bhardwaj G., Gerlach J. H., Mackie J. E., Grant C. E., Almquist K. C., Stewart A. J., Kurz E. U., Duncan A. M., Deeley R. G. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992 Dec 4;258(5088):1650–1654. doi: 10.1126/science.1360704. [DOI] [PubMed] [Google Scholar]
  5. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  6. Fathallah-Shaykh H., Wolf S., Wong E., Posner J. B., Furneaux H. M. Cloning of a leucine-zipper protein recognized by the sera of patients with antibody-associated paraneoplastic cerebellar degeneration. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3451–3454. doi: 10.1073/pnas.88.8.3451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fuchshuber A., Deltas C. C., Berthold S., Stavrou C., Vollmer M., Burton C., Feest T., Krieter D., Gal A., Brandis M. Autosomal dominant medullary cystic kidney disease: evidence of gene locus heterogeneity. Nephrol Dial Transplant. 1998 Aug;13(8):1955–1957. doi: 10.1093/ndt/13.8.1955. [DOI] [PubMed] [Google Scholar]
  8. Gardner K. D., Jr Evolution of clinical signs in adult-onset cystic disease of the renal medulla. Ann Intern Med. 1971 Jan;74(1):47–54. doi: 10.7326/0003-4819-74-1-47. [DOI] [PubMed] [Google Scholar]
  9. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  10. Hildebrandt F., Otto E., Rensing C., Nothwang H. G., Vollmer M., Adolphs J., Hanusch H., Brandis M. A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nat Genet. 1997 Oct;17(2):149–153. doi: 10.1038/ng1097-149. [DOI] [PubMed] [Google Scholar]
  11. Hildebrandt F., Waldherr R., Kutt R., Brandis M. The nephronophthisis complex: clinical and genetic aspects. Clin Investig. 1992 Sep;70(9):802–808. doi: 10.1007/BF00180751. [DOI] [PubMed] [Google Scholar]
  12. Hosokawa Y., Suzuki H., Toda H., Nishikimi M., Ozawa T. Complementary DNA encoding core protein II of human mitochondrial cytochrome bc1 complex. Substantial diversity in deduced primary structure from its yeast counterpart. J Biol Chem. 1989 Aug 15;264(23):13483–13488. [PubMed] [Google Scholar]
  13. Kim R. Y., Gasser R., Wistow G. J. mu-crystallin is a mammalian homologue of Agrobacterium ornithine cyclodeaminase and is expressed in human retina. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9292–9296. doi: 10.1073/pnas.89.19.9292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Murray T., Goldberg M. Chronic interstitial nephritis: etiologic factors. Ann Intern Med. 1975 Apr;82(4):453–459. doi: 10.7326/0003-4819-82-4-453. [DOI] [PubMed] [Google Scholar]
  16. Neumann H. P., Zäuner I., Strahm B., Bender B. U., Schollmeyer P., Blum U., Rohrbach R., Hildebrandt F. Late occurrence of cysts in autosomal dominant medullary cystic kidney disease. Nephrol Dial Transplant. 1997 Jun;12(6):1242–1246. doi: 10.1093/ndt/12.6.1242. [DOI] [PubMed] [Google Scholar]
  17. Pennica D., Kohr W. J., Kuang W. J., Glaister D., Aggarwal B. B., Chen E. Y., Goeddel D. V. Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein. Science. 1987 Apr 3;236(4797):83–88. doi: 10.1126/science.3453112. [DOI] [PubMed] [Google Scholar]
  18. Pook M. A., Jeremiah S., Scheinman S. J., Povey S., Thakker R. V. Localization of the Tamm-Horsfall glycoprotein (uromodulin) gene to chromosome 16p12.3-16p13.11. Ann Hum Genet. 1993 Oct;57(Pt 4):285–290. doi: 10.1111/j.1469-1809.1993.tb00902.x. [DOI] [PubMed] [Google Scholar]
  19. Resnick J. S., Sisson S., Vernier R. L. Tamm-Horsfall protein. Abnormal localization in renal disease. Lab Invest. 1978 May;38(5):550–555. [PubMed] [Google Scholar]
  20. Saunier S., Calado J., Heilig R., Silbermann F., Benessy F., Morin G., Konrad M., Broyer M., Gubler M. C., Weissenbach J. A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis. Hum Mol Genet. 1997 Dec;6(13):2317–2323. doi: 10.1093/hmg/6.13.2317. [DOI] [PubMed] [Google Scholar]
  21. Scolari F., Ghiggeri G. M., Casari G., Amoroso A., Puzzer D., Caridi G. L., Valzorio B., Tardanico R., Vizzardi V., Savoldi S. Autosomal dominant medullary cystic disease: a disorder with variable clinical pictures and exclusion of linkage with the NPH1 locus. Nephrol Dial Transplant. 1998 Oct;13(10):2536–2546. doi: 10.1093/ndt/13.10.2536. [DOI] [PubMed] [Google Scholar]
  22. Shimkets R. A., Warnock D. G., Bositis C. M., Nelson-Williams C., Hansson J. H., Schambelan M., Gill J. R., Jr, Ulick S., Milora R. V., Findling J. W. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994 Nov 4;79(3):407–414. doi: 10.1016/0092-8674(94)90250-x. [DOI] [PubMed] [Google Scholar]
  23. Sikri K. L., Foster C. L., Bloomfield F. J., Marshall R. D. Localization by immunofluorescence and by light- and electron-microscopic immunoperoxidase techniques of Tamm-Horsfall glycoprotein in adult hamster kidney. Biochem J. 1979 Sep 1;181(3):525–532. doi: 10.1042/bj1810525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sohocki M. M., Sullivan L. S., Harrison W. R., Sodergren E. J., Elder F. F., Weinstock G., Tanase S., Daiger S. P. Human glutamate pyruvate transaminase (GPT): localization to 8q24.3, cDNA and genomic sequences, and polymorphic sites. Genomics. 1997 Mar 1;40(2):247–252. doi: 10.1006/geno.1996.4604. [DOI] [PubMed] [Google Scholar]
  25. Stavrou C., Pierides A., Zouvani I., Kyriacou K., Antignac C., Neophytou P., Christodoulou K., Deltas C. C. Medullary cystic kidney disease with hyperuricemia and gout in a large Cypriot family: no allelism with nephronophthisis type 1. Am J Med Genet. 1998 May 1;77(2):149–154. doi: 10.1002/(sici)1096-8628(19980501)77:2<149::aid-ajmg8>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  26. Voilley N., Bassilana F., Mignon C., Merscher S., Mattéi M. G., Carle G. F., Lazdunski M., Barbry P. Cloning, chromosomal localization, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-sensitive sodium channel. Genomics. 1995 Aug 10;28(3):560–565. doi: 10.1006/geno.1995.1188. [DOI] [PubMed] [Google Scholar]
  27. Zager R. A., Cotran R. S., Hoyer J. R. Pathologic localization of Tamm-Horsfall protein in interstitial deposits in renal disease. Lab Invest. 1978 Jan;38(1):52–57. [PubMed] [Google Scholar]

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