Established and candidate transthyretin amyloidosis variants identified in the Saudi population by data mining

Mohamed Abouelhoda, Dania Mohty, Islam Alayary, Brian F. Meyer, Stefan T. Arold, Bahaa M. Fadel, Dorota Monies

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
JournalHuman Genomics
Volume15
Issue number1
DOIs
StatePublished - Aug 11 2021

ASJC Scopus subject areas

  • Genetics
  • Drug Discovery
  • Molecular Medicine
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Established and candidate transthyretin amyloidosis variants identified in the Saudi population by data mining'. Together they form a unique fingerprint.

Cite this