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. PATIENTS AND 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.
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. PATIENTS AND 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 MTHFRC677T mutations). The pathogenic hypotheses of stroke in this family are considered.
Authors: B Wilcken; F Bamforth; Z Li; H Zhu; A Ritvanen; M Renlund; C Stoll; Y Alembik; B Dott; A E Czeizel; Z Gelman-Kohan; G Scarano; S Bianca; G Ettore; R Tenconi; S Bellato; I Scala; O M Mutchinick; M A López; H de Walle; R Hofstra; L Joutchenko; L Kavteladze; E Bermejo; M L Martínez-Frías; M Gallagher; J D Erickson; S E Vollset; P Mastroiacovo; G Andria; L D Botto; M Redlund Journal: J Med Genet Date: 2003-08 Impact factor: 6.318
Authors: A B Guttormsen; P M Ueland; I Nesthus; O Nygård; J Schneede; S E Vollset; H Refsum Journal: J Clin Invest Date: 1996-11-01 Impact factor: 14.808
Authors: P Frosst; H J Blom; R Milos; P Goyette; C A Sheppard; R G Matthews; G J Boers; M den Heijer; L A Kluijtmans; L P van den Heuvel Journal: Nat Genet Date: 1995-05 Impact factor: 38.330