title: Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.
abstract: Biotin-responsive basal ganglia disease (BBGD) is a recessive disorder with childhood onset that presents as a subacute encephalopathy, with confusion, dysarthria, and dysphagia, and that progresses to severe cogwheel rigidity, dystonia, quadriparesis, and eventual death, if left untreated. BBGD symptoms disappear within a few days with the administration of high doses of biotin (5-10 mg/kg/d). On brain magnetic resonance imaging examination, patients display central bilateral necrosis in the head of the caudate, with complete or partial involvement of the putamen. All patients diagnosed to date are of Saudi, Syrian, or Yemeni ancestry, and all have consanguineous parents. Using linkage analysis in four families, we mapped the genetic defect near marker D2S2158 in 2q36.3 (LOD=5.9; theta=0.0) to a minimum candidate region (approximately 2 Mb) between D2S2354 and D2S1256, on the basis of complete homozygosity. In this segment, each family displayed one of two different missense mutations that altered the coding sequence of SLC19A3, the gene for a transporter related to the reduced-folate (encoded by SLC19A1) and thiamin (encoded by SLC19A2) transporters.
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Charlestown, MA 02129-2000, USA.
authors.forename: Wen-Qi
authors.initials: WQ
authors.lastname: Zeng
authors.forename: Eiman
authors.initials: E
authors.lastname: Al-Yamani
authors.forename: James S
authors.initials: JS
authors.lastname: Acierno
authors.forename: Susan
authors.initials: S
authors.lastname: Slaugenhaupt
authors.forename: Tammy
authors.initials: T
authors.lastname: Gillis
authors.forename: Marcy E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: Pinar T
authors.initials: PT
authors.lastname: Ozand
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
mesh_terms: D001480:Basal Ganglia Diseases / Q000235:genetics*; D001483:Base Sequence; D001710:Biotin / Q000494:pharmacology*; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree
chemical_list: D026901:Membrane Transport Proteins; C492291:SLC19A3 protein, human; D001710:Biotin