Glut1 deficiency: inheritance pattern determined by haploinsufficiency.
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.
Rotstein
Michael
M
Colleen Giblin Laboratories for Pediatric Neurology Research, Columbia University, New York, NY, USA.
Engelstad
Kristin
K
Yang
Hong
H
Wang
Dong
D
Levy
Brynn
B
Chung
Wendy K
WK
De Vivo
Darryl C
DC
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
D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D019325:3-O-Methylglucose