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Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders

Item Type:Article
Title:Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders
Creators Name:Hasselbacher, K. and Wiggins, R.C. and Matejas, V. and Hinkes, B.G. and Mucha, B. and Hoskins, B.E. and Ozaltin, F. and Nuernberg, G. and Becker, C. and Hangan, D. and Pohl, M. and Kuwertz-Broeking, E. and Griebel, M. and Schumacher, V. and Royer-Pokora, B. and Bakkaloglu, A. and Nuernberg, P. and Zenker, M. and Hildebrandt, F.
Abstract:Congenital nephrotic syndrome is clinically and genetically heterogeneous. The majority of cases can be attributed to mutations in the genes NPHS1, NPHS2, and WT1. By homozygosity mapping in a consanguineous family with isolated congenital nephrotic syndrome, we identified a potential candidate region on chromosome 3p. The LAMB2 gene, which was recently reported as mutated in Pierson syndrome (microcoria-congenital nephrosis syndrome; OMIM #609049), was located in the linkage interval. Sequencing of all coding exons of LAMB2 revealed a novel homozygous missense mutation (R246Q) in both affected children. A different mutation at this codon (R246W), which is highly conserved through evolution, has recently been reported as causing Pierson syndrome. Subsequent LAMB2 mutational screening in six additional families with congenital nephrotic syndrome revealed compound heterozygosity for two novel missense mutations in one family with additional nonspecific ocular anomalies. These findings demonstrate that the spectrum of LAMB2-associated disorders is broader than previously anticipated and includes congenital nephrotic syndrome without eye anomalies or with minor ocular changes different from those observed in Pierson syndrome. This phenotypic variability likely reflects specific genotypes. We conclude that mutational analysis in LAMB2 should be considered in congenital nephrotic syndrome, if no mutations are found in NPHS1, NPHS2, or WT1.
Keywords:Nephrotic syndrome, Pierson syndrome, LAMB2, Autosomal recessive
Source:Kidney International
ISSN:0085-2538
Publisher:Nature Publishing Group (U.S.A.)
Volume:70
Number:6
Page Range:1008-1012
Date:2 September 2006
Official Publication:https://doi.org/10.1038/sj.ki.5001679
PubMed:View item in PubMed

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