Reappraisal of Variants Previously Linked with Sudden Infant Death Syndrome: Results from Three Population-based Cohorts

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2019 May 3

PMID 31043699

Citations 5

Authors

Christian Paludan-Muller

Jonas Ghouse

Oliver B Vad

Cecilie B Herfelt

Pia Lundegaard

Gustav Ahlberg

Nicole Schmitt

Jesper H Svendsen

Stig Haunso

Henning Bundgaard

Torben Hansen

Jorgen K Kanters

Morten S Olesen

Affiliations

Soon will be listed here.

Abstract

We aimed to investigate the pathogenicity of cardiac ion channel variants previously associated with SIDS. We reviewed SIDS-associated variants previously reported in databases and the literature in three large population-based cohorts; The ExAC database, the Inter99 study, and the UK Biobank (UKBB). Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Of the 92 SIDS-associated variants, 59 (64%) were present in ExAC, 18 (20%) in Inter99, and 24 (26%) in UKBB. Using the Inter99 cohort, we found no difference in J-point amplitude and QTc-interval between carriers and non-carriers for 14/18 variants. There was no difference in the risk of syncope (P = 0.32), malignant ventricular arrhythmia (P = 0.96), and all-cause mortality (P = 0.59) between carriers and non-carriers. The ACMG guidelines reclassified 75% of all variants as variant-of-uncertain significance, likely benign, and benign. We identified ~2/3 of variants previously associated with SIDS and found no significant associations with electrocardiographic traits, syncope, malignant ventricular arrhythmia, or all-cause mortality. These data indicate that many of these variants are not highly penetrant, monogenic causes of SIDS and underline the importance of frequent reappraisal of genetic variants to avoid future misdiagnosis.

Citing Articles

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A de novo BRPF1 variant in a case of Sudden Unexplained Death in Childhood.

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