| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nephrology Dialysis Transplantation, Vol 12, Issue 9 1900-1907, Copyright © 1997 by Oxford University Press
L Longa, F Scolari, A Brusco, C Carbonara, S Polidoro, B Valzorio, P Riegler, N Migone and R Maiorca
Background. The renal lesions in tuberous sclerosis
complex (TSC) consist in multiple angiomyolipomas, often associated with
cysts of variable size. Recently a few TSC patients with early-onset renal
cysts resembling the autosomal dominant polycystic kidney disease (ADPKD)
have been described. Virtually all of them showed deletions of both
TSC2 and PKD1 genes.
Methods. Two unrelated families in which TSC and PKD
co-segregate were investigated. 16p13.3-linked haplotype segregation,
Southern blot, pulsed field gel electrophoresis, and loss of heterozygosity
analyses were performed in both affected and unaffected family members.
Results. The proband from family 1 was first
recognized as presenting typical neurological signs and skin lesions of TSC
and multiple renal cysts at 12 years of age. Haemodialysis became necessary
at age 28. CT and MRI scans revealed multiple cysts in the liver and an
asymptomatic, 3-4 mm aneurysm of the middle cerebral artery. His mother,
who died at 47 of breast cancer, had ADPKD and reached the ESRD at 42. She
showed facial angiofibromas. Both patients carried a submicroscopic
germline deletion spanning the entire TSC2 gene and
the large majority of PKD1 coding sequence. In the
proband from family 2, the TSC diagnosis was made at 4 years. Enlarged
polycystic kidneys causing end-stage renal failure at 19 years was
observed. This patient carried a large germline, de
novo deletion involving the entire TSC2 and
PKD1 genes. In addition we could show in a renal
hamartoma from this subject the loss of heterozygosity of markers spanning
the TSC2 and PKD1 genes for the
residual, normal chromosome 16 of paternal origin.
Conclusions. The presence of a deletion involving
both TSC2 and PKD1 genes should
be considered in the clinical assessment of TSC children with an early
onset polycystic kidney disease, and more generally in all ADPKD patients
who develop end-stage renal failure prior to the fourth or fifth decade of
life. Finally, the occurrence of typical renal and extrarenal signs of
ADPKD in a PKD1 hemizygote individual seems to support
concept that a somatic inactivation of the residual
PKD1 gene is required for the development of the
cysts. Keywords: autosomal dominant polycystic kidney
disease; contiguous TSC2 and PKD1
gene syndrome; loss of heterozygosity analysis; tuberous sclerosis complex
ORIGINAL ARTICLES
A large TSC2 and PKD1 gene deletion is associated with renal and extrarenal signs of autosomal dominant polycystic kidney disease
CNR-CIOS and Dipartimento di Genetica, Biologia e Chimica Medica, Universita di Torino, Via Santena 19, 10126 Torino, Italy; Spedali Civili, Brescia, Italy; Servizio di Nefrologia, Ospedale Generale Regionale, Bolzano, Italy
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. M. Bonsib Renal Cystic Diseases and Renal Neoplasms: A Mini-Review Clin. J. Am. Soc. Nephrol., December 1, 2009; 4(12): 1998 - 2007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Y. Li, G. P. Cosgrove, and J. J. Swigris Dyspnea in a 43-Year-Old Woman With Polycystic Kidney Disease Chest, January 1, 2009; 135(1): 238 - 243. [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Hartman, D. Liu, J. T. Zilfou, V. Robb, T. Morrison, T. Watnick, and E. P. Henske The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway Hum. Mol. Genet., January 1, 2009; 18(1): 151 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bisceglia, C. Galliani, I. Carosi, A. Simeone, and D. Ben-Dor Tuberous Sclerosis Complex With Polycystic Kidney Disease of the Adult Type: the TSC2/ADPKD1 Contiguous Gene Syndrome International Journal of Surgical Pathology, October 1, 2008; 16(4): 375 - 385. [Abstract] [PDF]
|
|
|
|
 |
|
 P. D. Wilson Polycystic Kidney Disease N. Engl. J. Med., January 8, 2004; 350(2): 151 - 164. [Full Text] [PDF]
|
|
|
|
 |
|
 Y M Smulders, B H J Eussen, S Verhoef, and C H Wouters Large deletion causing the TSC2-PKD1 contiguous gene syndrome without infantile polycystic disease J. Med. Genet., February 1, 2003; 40(2): e17 - 17. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cai, J. I. Everitt, H. Kugo, J. Cook, E. Kleymenova, and C. L. Walker Polycystic Kidney Disease as a Result of Loss of the Tuberous Sclerosis 2 Tumor Suppressor Gene During Development Am. J. Pathol., February 1, 2003; 162(2): 457 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Harris Autosomal dominant polycystickidney disease: clues to pathogenesis Hum. Mol. Genet., September 1, 1999; 8(10): 1861 - 1866. [Abstract] [Full Text] [PDF]
|
|