title: Glut1 deficiency: inheritance pattern determined by haploinsufficiency.
abstract: Two families manifesting Glut1 deficiency syndrome (DS) as an autosomal recessive trait are described. In 1 family, a severely affected boy inherited a mutated allele from his asymptomatic heterozygous mother. A de novo mutation developed in the paternal allele, producing compound heterozygosity. In another family, 2 mildly affected sisters inherited mutations from their asymptomatic heterozygous consanguineous parents. Red blood cell glucose uptake residual activity, a surrogate of haploinsufficiency, correlated with the clinical severity. These cases demonstrate that Glut1 DS may present as an autosomal recessive trait. The clinical pattern of inheritance is determined by the relative pathogenicity of the mutation and the resulting degree of haploinsufficiency.
authors.affiliation: Colleen Giblin Laboratories for Pediatric Neurology Research, Columbia University, New York, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rotstein
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelstad
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D044882:Glucose Metabolism Disorders / Q000235:genetics*; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics; D057895:Haploinsufficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009460:Neurologic Examination; D009865:Oocytes; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014162:Transfection / Q000379:methods; D014981:Xenopus
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D019325:3-O-Methylglucose