title: A novel stop mutation in the EDNRB gene in a family with Hirschsprung's disease associated with multiple sclerosis.
abstract: OBJECTIVE
  We identified a girl with Hirschsprung's disease (HSCR) whose mother and grandmother had HSCR associated with multiple sclerosis (MS). The aim of this study was to outline mutations in HSCR-related genes and MS susceptibility alleles in these three individuals.
  
  
  METHODS
  The phenotypes were reviewed based on medical records. The three subjects had rectosigmoid HSCR verified with histopathology. The mother and grandmother fulfilled the McDonald criteria for MS. DNA was isolated from EDTA-preserved blood according to standard procedures. Exome sequencing aiming mainly at analyzing HSCR associated genes as well as Sanger sequencing for confirmation was performed.
  
  
  RESULTS
  All affected individuals carry a novel heterozygous nonsense mutation in the EDNRB gene (c.C397T,p.R133X,refNM_000115), changing an arginine at position 133 into a premature stop codon. None of the subjects were homozygous for the HLA risk alleles for MS.
  
  
  CONCLUSIONS
  We report a novel non-sense EDNRB gene mutation in a girl with HSCR and her mother and grandmother with HSCR and MS. We propose that this EDNRB gene mutation plays a role in the etiology of HSCR and also makes the subjects susceptible to MS.
authors.affiliation: Division for Pediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska, University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna Löf
authors.initials: AL
authors.lastname: Granström
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ellen
authors.initials: E
authors.lastname: Markljung
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology Huddinge, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fink
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Edvard
authors.initials: E
authors.lastname: Nordenskjöld
authors.affiliation: Science for Life Laboratory, Department of Cell and Molecular Biology, Karolinska, Institutet, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nilsson
authors.affiliation: Division for Pediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska, University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. Electronic address: tomas.wester@karolinska.se.
authors.forename: Tomas
authors.initials: T
authors.lastname: Wester
authors.affiliation: Division for Pediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska, University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordenskjöld
mesh_terms: D000328:Adult; D018389:Codon, Nonsense; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000150:complications / Q000235:genetics*; D006801:Humans; D007223:Infant; D009103:Multiple Sclerosis / Q000150:complications / Q000235:genetics*; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; C000588596:EDNRB protein, human; D005819:Genetic Markers; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin
keywords: EDNRB gene; Hirschsprung’s disease; Multiple sclerosis