TY - JOUR
T1 - Penetrance estimation of TTR familial amyloid polyneuropathy (type I) in Brazilian families
AU - Saporta, M. A.C.
AU - Zaros, C.
AU - Cruz, M. W.
AU - André, C.
AU - Misrahi, M.
AU - Bonaïti-Pellié, C.
AU - Planté-Bordeneuve, V.
PY - 2009/3/1
Y1 - 2009/3/1
N2 - Background and purpose: Familial amyloid polyneuropathy (FAP) type I is a severe autosomal dominant inherited neuropathy associated with mutations in the transthyretin (TTR) gene. Significant phenotypic variability is seen amongst families with distinct geographic origin, especially regarding penetrance and age of onset. The aim of this study was to estimate the penetrance of FAP in Brazilian families. Methods: Twenty-two distinct families were ascertained through genetically confirmed index cases and included in this study. Genealogical and clinical data were obtained from a total of 623 individuals, including 126 affected by FAP. In 15 families, TTR genotyping was performed in all available relatives (n = 86), after informed written consent. Seven families did not consent for genetic testing, but agreed to provide clinical and genealogical data. Penetrance was estimated using a previously described method based on survival analysis and corrected for ascertainment bias. Results: Mean age of onset in our sample was 34.5 years, with a significant earlier onset in males (31.1 vs. 35.9, P < 0.0001). The penetrance of FAP in our sample was estimated as 83% (95% CI: 66-99) after 60 years. Conclusion: Our results provide new information on FAP in Brazilian patients and may be helpful in the genetic counseling of this population.
AB - Background and purpose: Familial amyloid polyneuropathy (FAP) type I is a severe autosomal dominant inherited neuropathy associated with mutations in the transthyretin (TTR) gene. Significant phenotypic variability is seen amongst families with distinct geographic origin, especially regarding penetrance and age of onset. The aim of this study was to estimate the penetrance of FAP in Brazilian families. Methods: Twenty-two distinct families were ascertained through genetically confirmed index cases and included in this study. Genealogical and clinical data were obtained from a total of 623 individuals, including 126 affected by FAP. In 15 families, TTR genotyping was performed in all available relatives (n = 86), after informed written consent. Seven families did not consent for genetic testing, but agreed to provide clinical and genealogical data. Penetrance was estimated using a previously described method based on survival analysis and corrected for ascertainment bias. Results: Mean age of onset in our sample was 34.5 years, with a significant earlier onset in males (31.1 vs. 35.9, P < 0.0001). The penetrance of FAP in our sample was estimated as 83% (95% CI: 66-99) after 60 years. Conclusion: Our results provide new information on FAP in Brazilian patients and may be helpful in the genetic counseling of this population.
KW - Brazil
KW - Familial amyloid polyneuropathy
KW - Penetrance
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U2 - 10.1111/j.1468-1331.2008.02429.x
DO - 10.1111/j.1468-1331.2008.02429.x
M3 - Article
C2 - 19364362
AN - SCOPUS:60049083978
VL - 16
SP - 337
EP - 341
JO - European Journal of Neurology
JF - European Journal of Neurology
SN - 1351-5101
IS - 3
ER -