Lessons learned from testing cardiac channelopathy and cardiomyopathy genes in individuals who died suddenly: A two‐year prospective study in a large medical examiner’s office with an in‐house molecular genetics laboratory and genetic counseling services

This is a comprehensive review and analysis of 254 cases tested consecutively in the in‐house College of American Pathologist‐accredited molecular genetics laboratory within the New York City Office of Chief Medical Examiner between October 2015 and February 2018, using a multigene cardiac panel com...

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Published in:Journal of genetic counseling 2020-04, Vol.29 (2), p.293-302
Main Authors: Williams, Nori, Manderski, Elizabeth, Stewart, Sarah, Bao, Ruijun, Tang, Yingying
Format: Article
Language:English
Subjects:
Adolescent
Adult
Arrhythmia
Arteriosclerosis
Atherosclerosis
Autopsy
Cardiac arrhythmia
cardiac genes
Cardiomyopathies - genetics
Cardiomyopathy
Cardiovascular diseases
Channelopathies - genetics
Channelopathy
Child
Child, Preschool
Coroners and Medical Examiners
Counseling services
Death, Sudden, Cardiac
Demography
Examiners
Female
Genes
Genetic Counseling
Genetic Predisposition to Disease
Genetic screening
Genetic Testing
Heart
Humans
Hypertension
Hypertrophy
Infant
Infants
Laboratories
Male
Medical examiners
Medical history
Molecular genetics
Pacific Islander people
panel testing
postmortem
Prospective Studies
public health
Referrals
Ryanodine receptors
Substance abuse
Substance use
Sudden death
underrepresented populations
Variants
Young Adult
Young adults
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cited_by cdi_FETCH-LOGICAL-c3537-b268e5be33b86ea93a35c8e25d6d30aba633be5cca3450da2d39fdb45a02250c3
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container_issue 2
container_start_page 293
container_title Journal of genetic counseling
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creator Williams, Nori
Manderski, Elizabeth
Stewart, Sarah
Bao, Ruijun
Tang, Yingying
description This is a comprehensive review and analysis of 254 cases tested consecutively in the in‐house College of American Pathologist‐accredited molecular genetics laboratory within the New York City Office of Chief Medical Examiner between October 2015 and February 2018, using a multigene cardiac panel composed of 95 genes associated with cardiac channelopathy and cardiomyopathy. Demographics, autopsy findings, medical history, and postmortem genetic testing results were collected for each case. The majority of decedents were adults (>25 years old, 52.7%), followed by infants (
doi_str_mv 10.1002/jgc4.1157
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Demographics, autopsy findings, medical history, and postmortem genetic testing results were collected for each case. The majority of decedents were adults (&gt;25 years old, 52.7%), followed by infants (&lt;12 months, 25.6%), young adults (19–25 years old, 11.4%), and children (1–18 years old, 10.2%). There were more males (64.2%) than females (35.8%). The racial/ethnic composition of decedents was 40.2% Black, 29.9% Hispanic, 22.4% White, 5.1% Asian/Pacific Islander, and 2.8% mixed/unspecified. Overall, 45.7% of decedents had a negative autopsy, and the remaining had one to four cardiac findings (cardiac hypertrophy, dilation, atherosclerosis, and fatty change). Twenty‐seven pathogenic/likely pathogenic variants (P/LP) and 99 variants of uncertain significance (VUS) were identified in 10.6% and 39% of decedents respectively. P/LP and VUS were found in 51 cardiac genes of the total 95 genes, where MYBPC3, TTN (predicted truncating variants), KCNH2, RYR2 and DSP genes had more than two P/LP variants identified. Among the 73 decedents who were suspected of having cardiac arrhythmia or cardiomyopathy, 20.3% had P/LP variants and 47.9% had VUS; among 23 decedents who had hypertensive cardiovascular diseases and 20 decedents with a history of substance use, 13% and 30% had P/LP variants, respectively. There were 26 referrals from medical examiners for genetic counseling and the outcomes are discussed. 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Demographics, autopsy findings, medical history, and postmortem genetic testing results were collected for each case. The majority of decedents were adults (&gt;25 years old, 52.7%), followed by infants (&lt;12 months, 25.6%), young adults (19–25 years old, 11.4%), and children (1–18 years old, 10.2%). There were more males (64.2%) than females (35.8%). The racial/ethnic composition of decedents was 40.2% Black, 29.9% Hispanic, 22.4% White, 5.1% Asian/Pacific Islander, and 2.8% mixed/unspecified. Overall, 45.7% of decedents had a negative autopsy, and the remaining had one to four cardiac findings (cardiac hypertrophy, dilation, atherosclerosis, and fatty change). Twenty‐seven pathogenic/likely pathogenic variants (P/LP) and 99 variants of uncertain significance (VUS) were identified in 10.6% and 39% of decedents respectively. 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Demographics, autopsy findings, medical history, and postmortem genetic testing results were collected for each case. The majority of decedents were adults (&gt;25 years old, 52.7%), followed by infants (&lt;12 months, 25.6%), young adults (19–25 years old, 11.4%), and children (1–18 years old, 10.2%). There were more males (64.2%) than females (35.8%). The racial/ethnic composition of decedents was 40.2% Black, 29.9% Hispanic, 22.4% White, 5.1% Asian/Pacific Islander, and 2.8% mixed/unspecified. Overall, 45.7% of decedents had a negative autopsy, and the remaining had one to four cardiac findings (cardiac hypertrophy, dilation, atherosclerosis, and fatty change). Twenty‐seven pathogenic/likely pathogenic variants (P/LP) and 99 variants of uncertain significance (VUS) were identified in 10.6% and 39% of decedents respectively. P/LP and VUS were found in 51 cardiac genes of the total 95 genes, where MYBPC3, TTN (predicted truncating variants), KCNH2, RYR2 and DSP genes had more than two P/LP variants identified. Among the 73 decedents who were suspected of having cardiac arrhythmia or cardiomyopathy, 20.3% had P/LP variants and 47.9% had VUS; among 23 decedents who had hypertensive cardiovascular diseases and 20 decedents with a history of substance use, 13% and 30% had P/LP variants, respectively. There were 26 referrals from medical examiners for genetic counseling and the outcomes are discussed. The study demonstrates characteristics of the diverse population typically seen by medical examiners in an urban center and our results support a broader implementation of molecular testing in sudden death.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>31436011</pmid><doi>10.1002/jgc4.1157</doi><tpages>10</tpages></addata></record>
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source Applied Social Sciences Index & Abstracts (ASSIA); Wiley
subjects Adolescent
Adult
Arrhythmia
Arteriosclerosis
Atherosclerosis
Autopsy
Cardiac arrhythmia
cardiac genes
Cardiomyopathies - genetics
Cardiomyopathy
Cardiovascular diseases
Channelopathies - genetics
Channelopathy
Child
Child, Preschool
Coroners and Medical Examiners
Counseling services
Death, Sudden, Cardiac
Demography
Examiners
Female
Genes
Genetic Counseling
Genetic Predisposition to Disease
Genetic screening
Genetic Testing
Heart
Humans
Hypertension
Hypertrophy
Infant
Infants
Laboratories
Male
Medical examiners
Medical history
Molecular genetics
Pacific Islander people
panel testing
postmortem
Prospective Studies
public health
Referrals
Ryanodine receptors
Substance abuse
Substance use
Sudden death
underrepresented populations
Variants
Young Adult
Young adults
title Lessons learned from testing cardiac channelopathy and cardiomyopathy genes in individuals who died suddenly: A two‐year prospective study in a large medical examiner’s office with an in‐house molecular genetics laboratory and genetic counseling services
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