title: A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report.
abstract: BACKGROUND
  In addition to its role in cell adhesion and gene expression in the canonical Wingless/integrated Wnt signaling pathway, β-catenin also regulates genes that underlie the transmission of nerve impulses. Mutations of CTNNB1 (β-catenin) have recently been described in patients with a wide range of neurodevelopmental disorders (intellectual disability, microcephaly and other syndromic features). We for the first time associate CTNNB1 mutation with hyperekplexia identifying it as an additional candidate for consideration in patients with startle syndrome.
  
  
  METHODS
  We describe an 11 year old male Polish patient with a de novo nonsense mutation in CTNNB1 who in addition to the major features of CTNNB1-related syndrome including intellectual disability and microcephaly, exhibited hyperekplexia and apraxia of upward gaze. The patient became symptomatic at the age of 20 months exhibiting delayed speech and psychomotor development. Social and emotional development was normal but mild hyperactivity was noted. Episodic falls when startled by noise or touch were observed from the age of 8.5 years, progressively increasing but never with loss of consciousness. Targeted gene panel next generation sequencing (NGS) and patient-parents trio analysis revealed a heterozygous de novo nonsense mutation in exon 3 of CTNNB1 identifying a novel association of β-catenin with hyperekplexia.
  
  
  CONCLUSIONS
  We report for the first time a clear association of mutation in CTNNB1 with an atypical syndromic heperekplexia expanding the phenotype of CTNNB1-related syndrome. Consequently CTNNB1 should be added to the growing list of genes to be considered as a cause of startle disease or syndromic hyperekplexia.
authors.affiliation: Chair and Department of Child Neurology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Winczewska-Wiktor
authors.affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Sciences, ul. Rokietnicka 8, 60-608, Poznań, Poland. bstronka@gmail.com.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Badura-Stronka
authors.affiliation: Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Monies-Nowicka
authors.affiliation: Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Michal Maciej
authors.initials: MM
authors.lastname: Nowicki
authors.affiliation: Chair and Department of Child Neurology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Steinborn
authors.affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Sciences, ul. Rokietnicka 8, 60-608, Poznań, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Latos-Bieleńska
authors.affiliation: Department of Genetics, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Dorota
authors.initials: D
authors.lastname: Monies
mesh_terms: D002648:Child; D018389:Codon, Nonsense; D015870:Gene Expression; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D010641:Phenotype; D016750:Stiff-Person Syndrome / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D018389:Codon, Nonsense; D051176:beta Catenin
keywords: Hyperekplexia; Intellectual disability; Microcephaly; β-catenin