NDT Advance Access originally published online on August 18, 2006
Nephrology Dialysis Transplantation 2006 21(11):3283-3286; doi:10.1093/ndt/gfl463
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A syndrome comprising childhood-onset glomerular kidney disease and ocular abnormalities with progressive loss of vision is caused by mutated LAMB2
1Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany and 2Department of Paediatrics, Faculty of Medicine and Health Sciences, UAE University, Post Box 17666, Al Ain, United Arab Emirates
Correspondence and offprint requests to: Martin Zenker MD, Institute of Human Genetics, Schwabachanlage 10, 91054 Erlangen, Germany. Email: mzenker{at}humgenet.uni-erlangen.de
Background. Pierson syndrome (OMIM 609049 [OMIM] ) is a severe congenital oculorenal disorder with early lethality. The condition is caused by mutations in the LAMB2 gene leading to complete loss of function of the gene product laminin ß2, an essential component of the glomerular and other basement membranes.
Methods. We present a non-consanguineous family with seven offspring affected by childhood-onset nephrotic syndrome progressing to end-stage renal failure and ocular abnormalities including cataracts, anterior chamber and iris abnormalities, and progressive blindness due to retinal detachment. The LAMB2 gene was analysed in this family by direct sequencing.
Results. The disorder turned out to segregate with compound heterozygosity for two novel LAMB2 mutations, 
V79 and Q1728X. Whereas the mutation Q1728X is predicted to confer complete loss of function, V79 probably represents a hypomorphic allele, thus explaining the substantially milder phenotype in this family.
Conclusion. This observation demonstrates that the phenotypic spectrum of LAMB2-associated disorders is broader than previously anticipated, and suggests that milder, non-lethal phenotypes may be associated with mutations retaining some residual function.
Keywords: autosomal recessive; blindness; laminin; nephrotic syndrome; Pierson syndrome
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Zhao, J. Ding, F. Wang, Q. Fan, N. Guan, S. Wang, and Y. Zhang The first Chinese Pierson syndrome with novel mutations in LAMB2 Nephrol. Dial. Transplant., October 26, 2009; (2009) gfp563v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Machuca, G. Benoit, and C. Antignac Genetics of nephrotic syndrome: connecting molecular genetics to podocyte physiology Hum. Mol. Genet., October 15, 2009; 18(R2): R185 - R194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R A Maselli, J J Ng, J A Anderson, O Cagney, J Arredondo, C Williams, H B Wessel, H Abdel-Hamid, and R L Wollmann Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome J. Med. Genet., March 1, 2009; 46(3): 203 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Liew, P. Mitchell, T. Y. Wong, S. K. Iyengar, and J. J. Wang CKD Increases the Risk of Age-Related Macular Degeneration J. Am. Soc. Nephrol., April 1, 2008; 19(4): 806 - 811. [Abstract] [Full Text] [PDF]
|
|