title: Generalized epilepsy in a family with basal ganglia calcifications and mutations in SLC20A2 and CHRNB2.
abstract: BACKGROUND
  The genetic understanding of primary familial brain calcification (PFBC) has increased considerably in recent years due to the finding of causal genes like SLC20A2, PDGFRB and PDGFB. The phenotype of PFBC is complex and has as of yet been poorly delineated. The most common clinical presentations include movement disorders, cognitive symptoms and psychiatric conditions. We report a family including two sisters with brain calcifications due to a variant in SLC20A2 and generalized tonic-clonic seizures as the principal phenotypic trait.
  
  
  METHODS
  The affected siblings underwent whole exome sequencing and candidate variants and cosegregation in the family were validated by Sanger sequencing.
  
  
  RESULTS
  Both siblings and their asymptomatic father were heterozygous for a variant in SLC20A2. The siblings also had a variant in CHRNB2, a known epilepsy gene associated with autosomal dominant frontal lobe epilepsy, which they had inherited from the mother.
  
  
  CONCLUSIONS
  To our knowledge, the reported siblings represent the third and fourth subjects with confirmed SLC20A2 variants exhibiting epilepsy as a phenotypic trait. Our findings support seizures as part of the phenotypic spectrum of SLC20A2-related PFBC. However, the present phenotype may also result from additional genetic influence, such as the identified missense variant in CHRNB2.
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Kirkeveien 166, Bygg 25, Avdeling for Medisinsk Genetikk, Postboks 4956 Nydalen 0424 Oslo, Norway. Electronic address: roar.fjar@medisin.uio.no.
authors.forename: Roar
authors.initials: R
authors.lastname: Fjaer
authors.affiliation: Department of Neurology and Clinical Neurophysiology, St. Olav's University Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Eylert
authors.initials: E
authors.lastname: Brodtkorb
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Kirkeveien 166, Bygg 25, Avdeling for Medisinsk Genetikk, Postboks 4956 Nydalen 0424 Oslo, Norway.
authors.forename: Ane-Marte
authors.initials: AM
authors.lastname: Øye
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Kirkeveien 166, Bygg 25, Avdeling for Medisinsk Genetikk, Postboks 4956 Nydalen 0424 Oslo, Norway.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Kirkeveien 166, Bygg 25, Avdeling for Medisinsk Genetikk, Postboks 4956 Nydalen 0424 Oslo, Norway.
authors.forename: Magnus Dehli
authors.initials: MD
authors.lastname: Vigeland
authors.affiliation: Department of Medical Imaging, St. Olav's University Hospital, Trondheim, Norway.
authors.forename: Kjell Arne
authors.initials: KA
authors.lastname: Kvistad
authors.affiliation: Department of Microbiology, Oslo University Hospital, 0424 Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, 0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway.
authors.forename: Paul Hoff
authors.initials: PH
authors.lastname: Backe
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Kirkeveien 166, Bygg 25, Avdeling for Medisinsk Genetikk, Postboks 4956 Nydalen 0424 Oslo, Norway.
authors.forename: Kaja Kristine
authors.initials: KK
authors.lastname: Selmer
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001479:Basal Ganglia / Q000473:pathology*; D002114:Calcinosis; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D011978:Receptors, Nicotinic / Q000235:genetics*; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; C493589:SLC20A2 protein, human
keywords: CHRNB2; Digenic inheritance; Exome sequencing; Fahr's disease; Primary familial brain calcification; SLC20A2