title: A novel mutation of laminin β2 (LAMB2) in two siblings with renal failure.
abstract: 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 β2 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.
  
  
  CONCLUSIONS
  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. What is known • LAMB2 mutations are associated with Pierson syndrome • Pierson syndrome is associated with congenital nephrotic syndrome, microcoria and neurological deficits What is new • A novel mutation in the LAMB2 gene in two female siblings • Genotype and clinical phenotype description of a novel LAMB2 mutation.
authors.affiliation: Pediatric, University Medical Center Utrecht, Utrecht, The Netherlands. f.a.falix@amc.nl.
authors.forename: Farah A
authors.initials: FA
authors.lastname: Falix
authors.affiliation: Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Carlien A M
authors.initials: CA
authors.lastname: Bennebroek
authors.affiliation: Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: van der Zwaag
authors.affiliation: Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lapid-Gortzak
authors.affiliation: Pathology of the Emma Children's Hospital/Academic Medical Center, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.affiliation: Pediatric, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michiel J S
authors.initials: MJ
authors.lastname: Oosterveld
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D007797:Laminin / Q000235:genetics*; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital; D009392:Nephrectomy; D009404:Nephrotic Syndrome; D010641:Phenotype; D011681:Pupil Disorders; D051437:Renal Insufficiency / Q000473:pathology / Q000601:surgery*; D012160:Retina / Q000000981:diagnostic imaging / Q000473:pathology; D035781:Siblings; D041622:Tomography, Optical
chemical_list: D007797:Laminin; C058783:laminin beta2
keywords: LAMB2; Nephrotic syndrome; Ocular abnormalities; Pierson syndrome