Transthyretin Asn90 variant: amyloidogenic or non-amyloidogenic role.
A number of mutations were described in the TTR gene. They were generally related to a variety of inherited syndromes named 'familial TTR-related amyloidoses'. Although TTR mutations were mostly associated with familial amyloid polyneuropathy (FAP), these molecular variants were also found in patients with recurrent stroke, subarachnoidal bleeding and radiological findings of cerebral, cerebellar, cortical-subcortical infarctions and hemosiderosis. We describe a 46 y.o. man with recurrent cerebral haemorrhages carrying Asn90His variant of TTR gene. This mutation has been reported both in FAP and asymptomatic subjects raising the doubt on the possible amyloidogenetic role of this variant. The absence of mutation in the patient's father, who had a history of unexplained cerebral haemorrhage and the lack of symptoms and sign of cerebral bleeding in the two patient's sisters, carrying the same mutation, seem to support the hypothesis that His90Asn TTR mutation do not have an impact in amyloid formation. It has still to be established whether other gene variants in our patient could act synergistically with His90Asn TTR mutation in increasing the risk of CNS haemorrhages.
Bersano
A
A
Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, Milan, Italy. anna.bersano@unimi.it
Del Bo
R
R
Ballabio
E
E
Cinnante
C
C
Lanfranconi
S
S
Comi
G P
GP
Baron
P
P
Bresolin
N
N
Candelise
L
L
D000328:Adult; D019943:Amino Acid Substitution; D028227:Amyloid Neuropathies, Familial / Q000235:genetics*; D002545:Brain Ischemia / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020300:Intracranial Hemorrhages / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D011228:Prealbumin / Q000235:genetics* / Q000502:physiology; D012008:Recurrence
D011228:Prealbumin