A novel mutation of laminin [beta]2 (LAMB2) in two siblings with renal failure

• Published in: European journal of pediatrics 2017-04, Vol.176 (4), p.515
• Main Authors: Falix, Farah A, Bennebroek, Carlien Am, van der Zwaag, Bert, Lapid-gortzak, Ruth, Florquin, Sandrine, Oosterveld, Michiel Js
• Format: Article
• Language: English
• Subjects: Congenital diseases; Genotype & phenotype; Hemodialysis; Hypertension; Kidney diseases; Mutation; Myopia; Ostomy; Pediatrics; Proteins; Siblings; Steroids; Visual acuity
• ISSN: 0340-6199; 1432-1076
• DOI: 10.1007/s00431-017-2871-6

This report describes a novel mutation of LAMB2, the gene associated with Pierson syndrome (microcoria-congenital nephrosis syndrome), in two female siblings. The c.970T>C p.(Cys324Arg) mutation in the LAMB2 gene affects one of the eight highly conserved cysteine residues within the first EGF-like module of the laminin [beta]2 protein. These residues form disulfide bonds in order to achieve a correct 3D structure of the protein. The reported phenotype is considered a relatively mild variant of Pierson syndrome and is associated with later-onset (18 months) therapy-resistant nephrotic syndrome leading to renal failure, and ocular abnormalities consisting of high myopia, microcoria, diverse retinal abnormalities, hence a low level of visual acuity. Importantly, the reported LAMB2 mutation was associated with normal neurological development in both siblings. Conclusion : this report presents the variability of the renal, ocular and neurological phenotypes associated with LAMB2 mutations and underscores the importance of ophthalmologic examination in all children with unexplained renal insufficiency or nephrotic syndrome. [Table omitted.]