Two siblings with a homozygous MTHFR C677T (G80A-RFC1) mutation and stroke.
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.
Barbagallo
Massimo
M
Department of Pediatrics, University of Catania, Catania, Italy.
Pavone
Piero
P
Incorpora
Gemma
G
Domenico Praticò
Andrea
A
Romantshik
Olga
O
Friso
Simonetta
S
Spalice
Alberto
A
Nicita
Francesco
F
Polizzi
Agata
A
Ruggieri
Martino
M
Iannetti
Paola
P
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*
D042965:Methylenetetrahydrofolate Reductase (NADPH2)