A pedigree analysis with minimised ascertainment bias shows anticipation in Met30-transthyretin related familial amyloid polyneuropathy.
TLDR
Strong evidence is shown that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon and not all ascertainment biases could be eliminated.Abstract:
In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the affected parent in 68 parent-child pairs (including data on assumed age at onset and on asymptomatic obligate heterozygotes and parents at obligate 50% risk) in 15 families. Excluding the parent-child pairs involving the proband and "bilineal pairs", onset occurred earlier in the child than in the transmitting parent in 60 out of 68 "unilineal pairs". After correction for ascertainment bias resulting from incomplete penetrance and reduced biological fitness in early onset patients, the number of anticipation pairs (60 pairs) was still significantly larger than that of non-anticipation pairs (29.7 pairs) (p < 0.05). When the children were sons, the difference in age at onset was significantly greater in the mother-son pairs than in the father-son pairs (p = 0.023). Although not all ascertainment biases could be eliminated, these data show strong evidence that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon.read more
Citations
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Familial amyloid polyneuropathy
TL;DR: Oral administration of tafamidis meglumine, which prevents misfolding and deposition of mutated TTR, is under evaluation in patients with TTR FAP, and genetic counselling is recommended for the prevention of all types of FAP.
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THAOS – The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis
TL;DR: Quality of life in patients with hereditary TTR amyloidosis, but not asymptomatic carriers of disease-causing mutations, was severely impaired relative to that of the age-matched general US population.
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Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease.
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Familial transthyretin-type amyloid polyneuropathy in Japan: clinical and genetic heterogeneity.
TL;DR: Familial amyloid polyneuropathy (FAP) was once considered a disease peculiar to endemic areas, but it is now recognized not to be a rare disease among hereditary neuropathic disorders in Japan.
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