title: A novel LAMB2 gene mutation associated with a severe phenotype in a neonate with Pierson syndrome.
abstract: BACKGROUND
  Pierson syndrome (PS) is a rare autosomal recessive disorder, caused by mutations in the laminin β2 (LAMB2) gene. It is characterized by congenital nephrotic syndrome, microcoria, and neurodevelopmental deficits. Several mutations with genotype-phenotype correlations have been reported, often with great clinical variability. We hereby report a novel homozygous nonsense mutation in the LAMB2 gene, associated with a severe phenotype presentation.
  
  
  METHODS
  We describe a term male infant born from consanguineous parents. The mother previously lost three children in the neonatal period, secondary to undefined renal disease, had two spontaneous abortions, and gave birth to one healthy daughter. The index case presented at birth with bilateral microcoria, severe hypotonia, respiratory distress, and congenital nephrotic syndrome associated with anuria and severe renal failure requiring peritoneal dialysis. The patients' clinical follow-up was unfavorable, and the newborn died at 7 days of life, after withdrawal of life support. Genetic analysis revealed a homozygous nonsense mutation at position c.2890C>T causing a premature stop codon (p.R964*) in LAMB2 gene.
  
  
  CONCLUSIONS
  We here describe a novel nonsense homozygous mutation in LAMB2 gene causing a severe neonatal presentation of Pierson syndrome. This new mutation expands the genotype-phenotype spectrum of this rare disease and confirms that truncating mutations might be associated with severe clinical features.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland. boutaina.zemrani@chuv.ch.
authors.forename: Boutaina
authors.initials: B
authors.lastname: Zemrani
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Cachat
authors.affiliation: Service of Nephrology, Lausanne University Hospital, Rue du Bugnon 21, 1011, Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonny
authors.affiliation: Service of Neonatology, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Giannoni
authors.affiliation: Service of Ophthalmology, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
authors.forename: Jacques
authors.initials: J
authors.lastname: Durig
authors.affiliation: Service of Medical Genetics, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Fellmann
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Lausanne University Hospital, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
authors.forename: Hassib
authors.initials: H
authors.lastname: Chehade
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007797:Laminin / Q000235:genetics*; D008297:Male; D020294:Myasthenic Syndromes, Congenital; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D011681:Pupil Disorders / Q000235:genetics* / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: D018389:Codon, Nonsense; D007797:Laminin; C058783:laminin beta2
keywords: LAMB2 mutation; Nephrotic syndrome; Newborn; Pierson syndrome