A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia

Eur J Hum Genet. 2014 Oct;22(10):1236-8. doi: 10.1038/ejhg.2014.9. Epub 2014 Feb 12.

Abstract

Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case.

Publication types

  • Case Reports

MeSH terms

  • Basal Ganglia / pathology
  • Basal Ganglia Diseases / genetics*
  • Basal Ganglia Diseases / pathology
  • Brain / diagnostic imaging
  • Brain Diseases / genetics
  • Codon, Nonsense
  • DNA Topoisomerases, Type I / genetics
  • DNA Topoisomerases, Type I / metabolism
  • Dystonia / genetics*
  • Dystonia / pathology
  • Exons
  • Female
  • Humans
  • Laryngeal Diseases / genetics*
  • Laryngeal Diseases / pathology
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-sis / genetics*
  • Proto-Oncogene Proteins c-sis / metabolism
  • RNA Splicing Factors
  • Ribonucleoprotein, U2 Small Nuclear / genetics
  • Ribonucleoprotein, U2 Small Nuclear / metabolism
  • Tomography, X-Ray Computed
  • Young Adult

Substances

  • Codon, Nonsense
  • Proto-Oncogene Proteins c-sis
  • RNA Splicing Factors
  • Ribonucleoprotein, U2 Small Nuclear
  • SF3A1 protein, human
  • DNA Topoisomerases, Type I
  • TOP1 protein, human