Clinical testing panels for ALS: global distribution, consistency, and challenges

Allison A. Dilliott; Ahmad Al Nasser; Marwa Elnagheeb; Jennifer Fifita; Lyndal Henden; Ingrid M. Keseler; Steven Lenz; Heather Marriott; Emily Mccann; Maysen Mesaros; Sarah Opie-Martin; Emma Owens; Brooke Palus; Justyne Ross; Zhanjun Wang; Hannah White; Ammar Al-Chalabi; Peter M. Andersen; Michael Benatar; Ian Blair; Johnathan Cooper-Knock; Elizabeth A. Harrington; Jeannine Heckmann; John Landers; Cristiane Moreno; Melissa Nel; Evadnie Rampersaud; Jennifer Roggenbuck; Guy Rouleau; Bryan Traynor; Marka Van Blitterswijk; Wouter Van Rheenen; Jan Veldink; Jochen Weishaupt; Luke Drury; Matthew B. Harms; Sali M.K. Farhan

doi:10.1080/21678421.2023.2173015

Clinical testing panels for ALS: global distribution, consistency, and challenges

Allison A. Dilliott^*, Ahmad Al Nasser, Marwa Elnagheeb, Jennifer Fifita, Lyndal Henden, Ingrid M. Keseler, Steven Lenz, Heather Marriott, Emily Mccann, Maysen Mesaros, Sarah Opie-Martin, Emma Owens, Brooke Palus, Justyne Ross, Zhanjun Wang, Hannah White, Ammar Al-Chalabi, Peter M. Andersen, Michael Benatar, Ian BlairJohnathan Cooper-Knock, Elizabeth A. Harrington, Jeannine Heckmann, John Landers, Cristiane Moreno, Melissa Nel, Evadnie Rampersaud, Jennifer Roggenbuck, Guy Rouleau, Bryan Traynor, Marka Van Blitterswijk, Wouter Van Rheenen, Jan Veldink, Jochen Weishaupt, Luke Drury, Matthew B. Harms, Sali M.K. Farhan^*,

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS. Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests. Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes. Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.

Original language	English
Pages (from-to)	420-435
Number of pages	16
Journal	Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume	24
Issue number	5-6
DOIs	https://doi.org/10.1080/21678421.2023.2173015
Publication status	Published - Aug 2023

Keywords

Amyotrophic lateral sclerosis
clinical laboratories
gene panels
gene-disease relationships
genetic testing

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Clinical testing panels for ALS global distribution consistency and challengesFinal published version, 2.28 MBLicence: CC BY-NC-ND

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Dilliott, A. A., Al Nasser, A., Elnagheeb, M., Fifita, J., Henden, L., Keseler, I. M., Lenz, S., Marriott, H., Mccann, E., Mesaros, M., Opie-Martin, S., Owens, E., Palus, B., Ross, J., Wang, Z., White, H., Al-Chalabi, A., Andersen, P. M., Benatar, M. (2023). Clinical testing panels for ALS: global distribution, consistency, and challenges. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 24(5-6), 420-435. https://doi.org/10.1080/21678421.2023.2173015

@article{08e7805cb14243679645c534ec04f7da,

title = "Clinical testing panels for ALS: global distribution, consistency, and challenges",

abstract = "Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS. Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests. Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes. Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.",

keywords = "Amyotrophic lateral sclerosis, clinical laboratories, gene panels, gene-disease relationships, genetic testing",

author = "Dilliott, {Allison A.} and {Al Nasser}, Ahmad and Marwa Elnagheeb and Jennifer Fifita and Lyndal Henden and Keseler, {Ingrid M.} and Steven Lenz and Heather Marriott and Emily Mccann and Maysen Mesaros and Sarah Opie-Martin and Emma Owens and Brooke Palus and Justyne Ross and Zhanjun Wang and Hannah White and Ammar Al-Chalabi and Andersen, {Peter M.} and Michael Benatar and Ian Blair and Johnathan Cooper-Knock and Harrington, {Elizabeth A.} and Jeannine Heckmann and John Landers and Cristiane Moreno and Melissa Nel and Evadnie Rampersaud and Jennifer Roggenbuck and Guy Rouleau and Bryan Traynor and {Van Blitterswijk}, Marka and {Van Rheenen}, Wouter and Jan Veldink and Jochen Weishaupt and Luke Drury and Harms, {Matthew B.} and Farhan, {Sali M.K.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2023",

month = aug,

doi = "10.1080/21678421.2023.2173015",

language = "English",

volume = "24",

pages = "420--435",

journal = "Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration",

issn = "2167-8421",

publisher = "Informa Healthcare",

number = "5-6",

}

Dilliott, AA, Al Nasser, A, Elnagheeb, M, Fifita, J, Henden, L, Keseler, IM, Lenz, S, Marriott, H, Mccann, E, Mesaros, M, Opie-Martin, S, Owens, E, Palus, B, Ross, J, Wang, Z, White, H, Al-Chalabi, A, Andersen, PM, Benatar, M, Blair, I, Cooper-Knock, J, Harrington, EA, Heckmann, J, Landers, J, Moreno, C, Nel, M, Rampersaud, E, Roggenbuck, J, Rouleau, G, Traynor, B, Van Blitterswijk, M, Van Rheenen, W , Veldink, J, Weishaupt, J, Drury, L, Harms, MB, Farhan, SMK 2023, 'Clinical testing panels for ALS: global distribution, consistency, and challenges', Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol. 24, no. 5-6, pp. 420-435. https://doi.org/10.1080/21678421.2023.2173015

TY - JOUR

T1 - Clinical testing panels for ALS

T2 - global distribution, consistency, and challenges

AU - Dilliott, Allison A.

AU - Al Nasser, Ahmad

AU - Elnagheeb, Marwa

AU - Fifita, Jennifer

AU - Henden, Lyndal

AU - Keseler, Ingrid M.

AU - Lenz, Steven

AU - Marriott, Heather

AU - Mccann, Emily

AU - Mesaros, Maysen

AU - Opie-Martin, Sarah

AU - Owens, Emma

AU - Palus, Brooke

AU - Ross, Justyne

AU - Wang, Zhanjun

AU - White, Hannah

AU - Al-Chalabi, Ammar

AU - Andersen, Peter M.

AU - Benatar, Michael

AU - Blair, Ian

AU - Cooper-Knock, Johnathan

AU - Harrington, Elizabeth A.

AU - Heckmann, Jeannine

AU - Landers, John

AU - Moreno, Cristiane

AU - Nel, Melissa

AU - Rampersaud, Evadnie

AU - Roggenbuck, Jennifer

AU - Rouleau, Guy

AU - Traynor, Bryan

AU - Van Blitterswijk, Marka

AU - Van Rheenen, Wouter

AU - Veldink, Jan

AU - Weishaupt, Jochen

AU - Drury, Luke

AU - Harms, Matthew B.

AU - Farhan, Sali M.K.

PY - 2023/8

Y1 - 2023/8

N2 - Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS. Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests. Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes. Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.

AB - Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS. Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests. Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes. Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.

KW - Amyotrophic lateral sclerosis

KW - clinical laboratories

KW - gene panels

KW - gene-disease relationships

KW - genetic testing

UR - http://www.scopus.com/inward/record.url?scp=85150659766&partnerID=8YFLogxK

U2 - 10.1080/21678421.2023.2173015

DO - 10.1080/21678421.2023.2173015

M3 - Article

C2 - 36896705

AN - SCOPUS:85150659766

SN - 2167-8421

VL - 24

SP - 420

EP - 435

JO - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

JF - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

IS - 5-6

ER -

Clinical testing panels for ALS: global distribution, consistency, and challenges

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