Genetic testing in Polynesian long QT syndrome probands reveals a lower diagnostic yield and an increased prevalence of rare variants

Heart Rhythm. 2020 Aug;17(8):1304-1311. doi: 10.1016/j.hrthm.2020.03.015. Epub 2020 Mar 27.


Background: New Zealand has a multiethnic population and a national cardiac inherited disease registry (Cardiac Inherited Disease Registry New Zealand [CIDRNZ]). Ancestry is reflected in the spectrum and prevalence of genetic variants in long QT syndrome (LQTS).

Objective: The purpose of this study was to study the genetic testing yield and mutation spectrum of CIDRNZ LQTS probands stratified by self-identified ethnicity.

Methods: A 15-year retrospective review of clinical CIDRNZ LQTS probands with a Schwartz score of ≥2 who had undergone genetic testing was performed.

Results: Of the 264 included LQTS probands, 160 (61%) reported as European, 79 (30%) NZ Māori and Pacific peoples (Polynesian), and 25 (9%) Other ethnicities, with comparable clinical characteristics across ethnic groups (cardiac events in 72%; age at presentation 28±19 years; corrected QT interval 512±55 ms). Despite comparable testing (5.3±1.4 LQTS genes), a class III-V LQTS variant was identified in 35% of Polynesian probands as compared with 63% of European and 72% of Other probands (P<.0001). Among variant-positive CIDRNZ LQTS probands (n=148), Polynesians were more likely to have non-missense variants (57% vs 39% and 25% in probands of European and Other ethnicity, respectively; P=.005) as well as long QT syndrome type 1-3 variants not reported elsewhere (71% vs European 22% and Other 28%; P<.0001). Variants found in multiple probands were more likely to be shared within the same ethnic group; P<.01).

Conclusion: Genetic testing of Polynesian LQTS probands has a lower diagnostic yield, despite comparable testing and clinical disease severity. Rare LQTS variants are more common in Polynesian LQTS probands. These data emphasize the importance of increasing the knowledge of genetic variation in the Polynesian population.

Keywords: Ethnicity; Genetic testing; Genetic variation; Long QT syndrome; Mutation spectrum; Variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Forecasting*
  • Genetic Testing / methods*
  • Genotype
  • Humans
  • Long QT Syndrome / diagnosis*
  • Long QT Syndrome / ethnology
  • Male
  • Native Hawaiian or Other Pacific Islander*
  • New Zealand / epidemiology
  • Phenotype
  • Prevalence
  • Retrospective Studies

Supplementary concepts

  • Long Qt Syndrome 3