title: Two siblings with a homozygous MTHFR C677T (G80A-RFC1) mutation and stroke.
abstract: BACKGROUND
  Stroke is a rare disorder in childhood; among its risk factors, C677T mutations in the methylenetetrahydrofolate reductase (MTHFR) gene with secondary hyperhomocysteinemia are considered.
  
  
  METHODS
  We report on a family in which two brothers had arterial ischemic stroke (AIS). One of these siblings came to our observation at the age of 4 years because of decreased motility of the right arm, mild hypotrophy of the right limbs, and frequent falls: brain magnetic resonance imaging revealed a large left AIS. Family history revealed that his older brother had died at the age of 7 due to AIS. An extensive metabolic investigation revealed a homozygous C677T [G80A-reduced folate carrier 1 (RFC1)] mutation in the MTHFR gene in both the affected siblings and in their healthy older brother and heterozygous mutations in the parents. None of these family members presented hyperhomocysteinemia.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first family with multiple AIS patients harboring homozygous MTHFR gene C677T (G80A-RFC1) mutations without associated hyperhomocysteinemia (the latter factor is usually considered as effector of vascular damage in patients with MTHFR C677T mutations). The pathogenic hypotheses of stroke in this family are considered.
authors.affiliation: Department of Pediatrics, University of Catania, Catania, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Barbagallo
authors.forename: Piero
authors.initials: P
authors.lastname: Pavone
authors.forename: Gemma
authors.initials: G
authors.lastname: Incorpora
authors.forename: Andrea
authors.initials: A
authors.lastname: Domenico Praticò
authors.forename: Olga
authors.initials: O
authors.lastname: Romantshik
authors.forename: Simonetta
authors.initials: S
authors.lastname: Friso
authors.forename: Alberto
authors.initials: A
authors.lastname: Spalice
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicita
authors.forename: Agata
authors.initials: A
authors.lastname: Polizzi
authors.forename: Martino
authors.initials: M
authors.lastname: Ruggieri
authors.forename: Paola
authors.initials: P
authors.lastname: Iannetti
mesh_terms: D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005190:Family; D005838:Genotype; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000201:enzymology / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D035781:Siblings; D020521:Stroke / Q000201:enzymology / Q000235:genetics*
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)