title: A novel mutation of LAMB2 in a multigenerational mennonite family reveals a new phenotypic variant of Pierson syndrome.
abstract: OBJECTIVE
  To describe a novel laminin β-2 (LAMB2) mutation associated with nephrotic syndrome and severe retinal disease without microcoria in a large, multigenerational family with Pierson syndrome.
  
  
  METHODS
  Retrospective chart review and prospective family examination.
  
  
  METHODS
  An extended consanguineous family of 52 members.
  
  
  METHODS
  The eyes, urine, and serum DNA were evaluated in all family members after discovering 2 patients, both younger than 10 years, with bilateral retinal detachments and concurrent renal dysfunction. Linkage analysis was performed in the 9 living affected individuals, 7 using the Illumina Human Hap370 Duo Bead Array (Illumina, San Diego, CA) and 2 using GeneChip 10K (Affymetrix, Santa Clara, CA) mapping arrays.
  
  
  METHODS
  The prevalence and severity of ocular and kidney involvement and genetic findings.
  
  
  RESULTS
  Eleven affected family members were identified (9 living), all manifesting chronic kidney disease and bilateral chorioretinal pigmentary changes, with or without retinal detachments, but without microcoria or neurodevelopmental deficits, segregating in an autosomal recessive pattern. The causative gene was localized to a 9-Mb region on chromosome 3. Comprehensive gene sequencing revealed a novel LAMB2 variant (c.440A → G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1% in the Old Order Mennonite population, and absent in 91 non-Mennonite controls. The mutation is located in a highly conserved site in the N-terminal domain VI of LAMB2.
  
  
  CONCLUSIONS
  This study describes a novel mutation of LAMB2 and further expands the spectrum of eye and renal manifestations associated with defects in the laminin β-2 chain.
  
  
  BACKGROUND
  The author(s) have no proprietary or commercial interest in any materials discussed in this article.
authors.affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA. mohney@mayo.edu
authors.forename: Brian G
authors.initials: BG
authors.lastname: Mohney
authors.forename: Jose S
authors.initials: JS
authors.lastname: Pulido
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Marie C
authors.initials: MC
authors.lastname: Hogan
authors.forename: Mark B
authors.initials: MB
authors.lastname: Consugar
authors.forename: Justin
authors.initials: J
authors.lastname: Peters
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Samih H
authors.initials: SH
authors.lastname: Nasr
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Smith
authors.forename: James
authors.initials: J
authors.lastname: Gloor
authors.forename: Vickie
authors.initials: V
authors.lastname: Kubly
authors.forename: Dorothy
authors.initials: D
authors.lastname: Spencer
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nielson
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.forename: D Holmes
authors.initials: DH
authors.lastname: Morton
authors.forename: Lama
authors.initials: L
authors.lastname: Eldahdah
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020294:Myasthenic Syndromes, Congenital; D009404:Nephrotic Syndrome; D010375:Pedigree; D010641:Phenotype; D011681:Pupil Disorders / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007797:Laminin; C058783:laminin beta2; D004247:DNA