Onset in the seventh decade and lack of symptoms in heterozygotes for the TTRMet30 mutation in hereditary amyloid neuropathy—type I (Portuguese, Andrade)
Tóm tắt
In a Portuguese‐American family with hereditary amyloid neuropathy (familial amyloidotic polyneuropathy), onset was in the seventh decade in
Late onset and incomplete penetrance, at a clinical level, raise problems for presymptomatic detection of mutant TTR, as these tend to cluster in families. When counseling asymptomatic heterozygotes, we must consider intra‐familial correlation in age‐of‐onset, and the distribution of age‐of‐onset including age of unaffected heterozygotes.
This family poses interesting questions regarding pathogenesis of this degenerative process and the influence of other genetic factors, such as modifiers, epistasis, and polymorphism of the TTR genes or their regulators. A cis‐effect of a gene linked to the mutant gene, decreasing the synthesis of the mutant TTR and keeping a sufficient amount of the normal one in circulation, or producing some cofactor for TTR, could also explain late onset and apparently incomplete penetrance; the occasional finding of classic forms in these families would be the result of recombinatory events.
Từ khóa
Tài liệu tham khảo
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