title: Primary ciliary dyskinesia-causing mutations in Amish and Mennonite communities.
abstract: OBJECTIVE
  To determine whether individuals with primary ciliary dyskinesia (PCD) from unrelated Amish and Mennonite families harbor a single and unique founder mutation.
  
  
  METHODS
  Subjects from Amish and Mennonite communities in several states were enrolled in the study. All subjects were clinically characterized, and nasal nitric oxide levels were measured. Nasal epithelial scrapings were collected from several subjects for ciliary ultrastructural analyses. DNA was isolated from patients with PCD and their unaffected first- and second-degree relatives. Genome-wide homozygosity mapping, linkage analyses, targeted mutation analyses, and exome sequencing were performed.
  
  
  RESULTS
  All subjects from Old-Order Amish communities from Pennsylvania were homozygous for a nonsense mutant DNAH5 allele, c.4348C>T (p.Q1450X). Two affected siblings from an unrelated Mennonite family in Arkansas were homozygous for the same nonsense DNAH5 mutation. Children with PCD from an Amish family from Wisconsin had biallelic DNAH5 mutations, c.4348C>T (p.Q1450X) and c.10815delT (p.P3606HfsX23), and mutations in other genes associated with PCD were also identified in this community.
  
  
  CONCLUSIONS
  The Amish and Mennonite subjects from geographically dispersed and socially isolated communities had the same founder DNAH5 mutation, owing to the common heritage of these populations. However, disease-causing mutations in other PCD-associated genes were also found in affected individuals in these communities, illustrating the genetic heterogeneity in this consanguineous population.
authors.affiliation: Department of Pediatrics, Washington University in St Louis, St Louis, MO 63110, USA. ferkol_t@kids.wustl.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Ferkol
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
authors.forename: Hauw
authors.initials: H
authors.lastname: Lie
authors.forename: Cynthia
authors.initials: C
authors.lastname: Helms
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.forename: Anne
authors.initials: A
authors.lastname: Bowcock
authors.forename: John L
authors.initials: JL
authors.lastname: Carson
authors.forename: Milan
authors.initials: M
authors.lastname: Hazucha
authors.forename: D Holmes
authors.initials: DH
authors.lastname: Morton
authors.forename: Anand C
authors.initials: AC
authors.lastname: Patel
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Leigh
authors.forename: Michael R
authors.initials: MR
authors.lastname: Knowles
authors.forename: Maimoona A
authors.initials: MA
authors.lastname: Zariwala
mesh_terms: D000293:Adolescent; D061365:Amish / Q000235:genetics*; D001131:Arkansas; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007619:Kartagener Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010414:Pennsylvania; D014922:Wisconsin
keywords: NO; Nitric oxide; PCD; Primary ciliary dyskinesia