title: Mutation analysis of the motor neuron and pancreas homeobox 1 (MNX1, former HLXB9) gene in Swedish patients with Currarino syndrome.
abstract: BACKGROUND
  Currarino syndrome (CS) is a triad consisting of partial sacral agenesis, presacral mass, and anorectal malformations, typically anal stenosis but the phenotype varies. The main cause of this monogenic disorder is mutations in the motor neuron and pancreas homeobox 1 gene. We describe the clinical and genetic findings in 4 unrelated Swedish cases with CS and their relatives.
  
  
  METHODS
  We performed mutation analysis of the motor neuron and pancreas homeobox 1 gene in 4 cases with CS by DNA sequence analysis as well as multiplex ligation-dependent probe amplification. In addition, array comparative genome hybridization was performed in 2 cases. Including relatives, totally, 14 individuals were analyzed.
  
  
  RESULTS
  We found 2 previously described mutations, 1 de novo nonsense mutation (p.Gln212X) and 1 maternally inherited frameshift mutation (p.Pro18ProfsX38). In the family with the frameshift mutation, we also detected the same maternally inherited mutation in 3 of the proband's 4 brothers, who displayed varying symptoms. All mutation carriers had presacral tumors, although 2 were asymptomatic.
  
  
  CONCLUSIONS
  Our findings emphasize the need for genetic counseling and mutation analysis in patients with CS to detect tumors early. It shows the importance of evaluation of the sacrum and the presacral region in patients with anal stenosis with or without funnel anus. Family members of index cases should be considered for evaluation even if they are asymptomatic.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17176 Stockholm, Sweden.
authors.forename: Shulu
authors.initials: S
authors.lastname: Zu
authors.forename: Johanna
authors.initials: J
authors.lastname: Winberg
authors.forename: Fabian
authors.initials: F
authors.lastname: Arnberg
authors.forename: Gabriella
authors.initials: G
authors.lastname: Palmer
authors.forename: Pär-Johan
authors.initials: PJ
authors.lastname: Svensson
authors.forename: Tomas
authors.initials: T
authors.lastname: Wester
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordenskjöld
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D001003:Anal Canal / Q000002:abnormalities; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D057210:Delayed Diagnosis; D004065:Digestive System Abnormalities / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008588:Meningocele / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D012007:Rectum / Q000002:abnormalities; D012447:Sacrum / Q000002:abnormalities; D013548:Sweden / Q000453:epidemiology; D013595:Syringomyelia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D013724:Teratoma / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D018398:Homeodomain Proteins; C490003:MNX1 protein, human; D014157:Transcription Factors