Abstract
Background: Familial transthyretin (TTR) amyloidosis (ATTR) is an autosomal dominant disease with significant
phenotypic heterogeneity. Its prevalence in Saudi Arabia has not previously been investigated. An existing exome
variant database of Saudi individuals, sequenced to globally investigate rare diseases in the population, was mined
for TTR variants and filtered for missense mutations resulting in single amino acid changes. A total of 13,906 Saudi
exomes from unrelated individuals were analyzed blindly.
Results: Three TTR variants known to be associated with ATTR amyloidosis were identified. Additionally, three novel
TTR mutations were identified. Structural analysis of the three novel variants suggests that at least two could be
amyloidogenic. The most common variant associated with amyloidosis was p.Val142Ile (allele frequency 0.001).
Further investigation of these variants and their translation to clinical practice may help to diagnose, monitor, and
manage patients with ATTR amyloidosis.
Conclusion: Multiple TTR variants potentially associated with systemic ATTR amyloidosis were identified in the Saudi
population. Early diagnosis and intervention, facilitated by familial genetic testing of patients with ATTR amyloidosis,
may benefit in the management of this disease. Early diagnosis could be enhanced through inclusion of ATTR
variants in existing population-based screening programs.
Keywords: Transthyretin, Amyloidosis, Familial, Saudi population, Epidemiology
Original language | English (US) |
---|---|
Journal | Human Genomics |
Volume | 15 |
Issue number | 1 |
DOIs | |
State | Published - Aug 11 2021 |
ASJC Scopus subject areas
- Genetics
- Drug Discovery
- Molecular Medicine
- Molecular Biology