Journal of the American Society of Nephrology, Vol 4, 1371-1378, Copyright © 1993 by American Society of Nephrology

REGULAR ARTICLES

A kindred exhibiting cosegregation of an overlap connective tissue disorder and the chromosome 16 linked form of autosomal dominant polycystic kidney disease

S Somlo, G Rutecki, LA Giuffra, ST Reeders, A Cugino and FC Whittier
Albert Einstein College of Medicine, Division of Nephrology, Bronx, NY.

Autosomal dominant polycystic kidney disease (ADPKD) is a disorder of adult onset manifested by bilaterally enlarged cystic kidneys frequently associated with progressive renal failure. The mutated gene (PKD1) responsible for 85 to 95% of cases has been localized to a small segment on the distal tip of the short arm of chromosome 16. A clinical spectrum of heritable connective tissue disorders that remain unclassifiable under the present nosology but that contain elements of the Marfan's syndrome have previously been described. The genetic localization and molecular basis of such overlap connective tissue disorders (OCTD) have not been elucidated. In this report, a kindred in which ADPKD and OCTD appear to cosegregate is described. The connective tissue phenotype in this family includes aortic root dilation, aortic and vertebral artery aneurysms with dissection, and aortic valve incompetence, as well as pectus abnormalities, pes planus, joint laxity, arachnodactyly, scoliosis, dolichostenomelia, and high arched palate. ADPKD was manifest primarily as bilateral renal cysts with or without renal failure. The DNA of all living family members was studied with markers recognizing polymorphic loci flanking the PKD1 region (3'HVR and O90a), as well as markers from the loci of chromosomes 15 and 5, associated with fibrillin genes FBN1 and FBN2, respectively. In this kindred of 20 family members traced through five generations, cosegregation of ADPKD and the OCTD phenotype was observed in 12 of 12 meioses and 3 of 3 phase known. Both markers for PKD1 were tightly linked to both ADPKD and OCTD, whereas there was no evidence for linkage with either fibrillin locus. In this family, the ADPKD and OCTD mutations are genetically linked. The presence of OCTD with ADPKD identifies a group of patients at significantly greater risk for sudden death from aortic root and other vascular aneurysmal dissection and rupture.

This article has been cited by other articles:

				Q. Qian, R. P. Hartman, B. F. King, and V. E. Torres Increased Occurrence of Pericardial Effusion in Patients with Autosomal Dominant Polycystic Kidney Disease Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1223 - 1227. [Abstract] [Full Text] [PDF]

				W Al-Hakim and D J A Goldsmith Bilateral popliteal aneurysms complicating adult polycystic kidney disease in a patient with a marfanoid habitus Postgrad. Med. J., August 1, 2003; 79(934): 474 - 475. [Abstract] [Full Text] [PDF]

				C. Boulter, S. Mulroy, S. Webb, S. Fleming, K. Brindle, and R. Sandford Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene PNAS, September 26, 2001; (2001) 211191098. [Abstract] [Full Text] [PDF]

				A. Strassburg, E. Schirg, and J. H. H. Ehrich A child with polycystic kidney disease: do we have to care about associated malformations? Nephrol. Dial. Transplant., September 1, 2001; 16(9): 1942 - 1944. [Full Text] [PDF]

				D. Guo, S. Hasham, S.-Q. Kuang, C. J. Vaughan, E. Boerwinkle, H. Chen, D. Abuelo, H. C. Dietz, C. T. Basson, S. S. Shete, et al. Familial Thoracic Aortic Aneurysms and Dissections : Genetic Heterogeneity With a Major Locus Mapping to 5q13-14 Circulation, May 22, 2001; 103(20): 2461 - 2468. [Abstract] [Full Text] [PDF]

				V. E. TORRES, Y. CAI, X. CHEN, G. Q. WU, L. GENG, K. A. CLEGHORN, C. M. JOHNSON, and S. SOMLO Vascular Expression of Polycystin-2 J. Am. Soc. Nephrol., January 1, 2001; 12(1): 1 - 9. [Abstract] [Full Text]

				A. C. M. Ong, C. J. Ward, R. J. Butler, S. Biddolph, C. Bowker, R. Torra, Y. Pei, and P. C. Harris Coordinate Expression of the Autosomal Dominant Polycystic Kidney Disease Proteins, Polycystin-2 And Polycystin-1, in Normal and Cystic Tissue Am. J. Pathol., June 1, 1999; 154(6): 1721 - 1729. [Abstract] [Full Text] [PDF]

				W. I. Schievink, B. Mokri, D. G. Piepgras, and J. D. Kuiper Recurrent Spontaneous Arterial Dissections : Risk in Familial Versus Nonfamilial Disease Stroke, April 1, 1996; 27(4): 622 - 624. [Abstract] [Full Text]

				W. I. Schievink and B. Mokri Familial Aorto-Cervicocephalic Arterial Dissections and Congenitally Bicuspid Aortic Valve Stroke, October 1, 1995; 26(10): 1935 - 1940. [Abstract] [Full Text]

				W. I. Schievink, V. V. Michels, B. Mokri, D. G. Piepgras, and H. O. Perry A Familial Syndrome of Arterial Dissections with Lentiginosis N. Engl. J. Med., March 2, 1995; 332(9): 576 - 579. [Full Text] [PDF]

				C. Boulter, S. Mulroy, S. Webb, S. Fleming, K. Brindle, and R. Sandford Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene PNAS, October 9, 2001; 98(21): 12174 - 12179. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673