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Updated: May 19, 2026
06:33
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Familial amyloidosis with polyneuropathy associated with TTR Ser50Arg mutation
Alejandra González-Duarte1, Karla Cárdenas Soto, Deborah Martínez-Baños
1Department of Neurology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico DF. gonzalezduarte@aol.com
Summary
The transthyretin amyloidosis (ATTR) Ser50Arg mutation leads to early disease onset and affects men more severely. Later generations show symptoms at younger ages, indicating potential anticipation.
Area of Science:
- Genetics
- Neurology
- Rare Diseases
Background:
- Phenotypic heterogeneity in transthyretin amyloidosis (ATTR) familial polyneuropathy is influenced by mutation type and environment.
- A gender disparity in disease severity has been suggested.
- Over 100 pathogenic variants of hereditary transthyretin (TTR) mutations are documented.
Purpose of the Study:
- To characterize 32 patients with the TTR Ser50Arg mutation from a single geographic region.
- To investigate the clinical presentation and genetic transmission of ATTR Ser50Arg.
Main Methods:
- Genetic testing and prospective clinical/laboratory evaluations were performed on seven families across multiple generations.
- Analysis included confirmation of the TTR Ser50Arg mutation in affected individuals and relatives.
Main Results:
- The TTR Ser50Arg mutation was confirmed in 32 individuals (18 men, 56%).
- Early symptom onset occurred between ages 36-41, with later generations presenting earlier.
- Men exhibited a worse disease outcome compared to women; initial symptoms were primarily neuropathic (70%).
Conclusions:
- The ATTR Ser50Arg mutation is linked to early onset and an increased prevalence in males.
- Males experience a more aggressive disease course.
- Evidence suggests possible anticipation, where subsequent generations are affected at younger ages.
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