International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma

Laurene Ben Aim; Eamonn R. Maher; Alberto Cascon; Anne Barlier; Sophie Giraud; Tonino Ercolino; Pascal Pigny; Roderick J. Clifton-Bligh; Delphine Mirebeau-Prunier; Amira Mohamed; Judith Favier; Anne-Paule Gimenez-Roqueplo; Francesca Schiavi; Rodrigo A. Toledo; Patricia L. Dahia; Mercedes Robledo; Nelly Burnichon

doi:10.1136/jmedgenet-2020-107652

International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma

Laurene Ben Aim, Eamonn R. Maher, Alberto Cascon, Anne Barlier, Sophie Giraud, Tonino Ercolino, Pascal Pigny, Roderick J. Clifton-Bligh, Delphine Mirebeau-Prunier, Amira Mohamed, Judith Favier, Anne-Paule Gimenez-Roqueplo, Francesca Schiavi, Rodrigo A. Toledo, Patricia L. Dahia, Mercedes Robledo, Nelly Burnichon

Aston Medical School

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

Abstract

BACKGROUND: SDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the 'NGS and PPGL (NGSnPPGL) Study Group' initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database.

METHODS: A total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field.

RESULTS: This multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system (https://databases.lovd.nl/shared/genes/SDHB).

CONCLUSION: This international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.

Original language	English
Pages (from-to)	785-792
Number of pages	8
Journal	Journal of Medical Genetics
Volume	59
Issue number	8
Early online date	27 Aug 2021
DOIs	https://doi.org/10.1136/jmedgenet-2020-107652
Publication status	Published - 21 Jul 2022

Bibliographical note

Copyright © Author(s) (or their employer(s)), 2022. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

Keywords

Adrenal Gland Neoplasms/genetics
Genetic Testing
Germ-Line Mutation/genetics
Humans
Paraganglioma/diagnosis
Pheochromocytoma/diagnosis
Succinate Dehydrogenase/genetics

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10.1136/jmedgenet-2020-107652Licence: CC BY 4.0

L Ben Aim et al_International initiative curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma.full
Copyright © Author(s) (or their employer(s)), 2022. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Final published version, 1.07 MBLicence: CC BY 4.0

Cite this

Ben Aim, L., Maher, E. R., Cascon, A., Barlier, A., Giraud, S., Ercolino, T., Pigny, P., Clifton-Bligh, R. J., Mirebeau-Prunier, D., Mohamed, A., Favier, J., Gimenez-Roqueplo, A.-P., Schiavi, F., Toledo, R. A., Dahia, P. L., Robledo, M., & Burnichon, N. (2022). International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma. Journal of Medical Genetics, 59(8), 785-792. https://doi.org/10.1136/jmedgenet-2020-107652

@article{350447f31b3648e3a1ceef3f91557abc,

title = "International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma",

abstract = "BACKGROUND: SDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the 'NGS and PPGL (NGSnPPGL) Study Group' initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database.METHODS: A total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field.RESULTS: This multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system (https://databases.lovd.nl/shared/genes/SDHB).CONCLUSION: This international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.",

keywords = "Adrenal Gland Neoplasms/genetics, Genetic Testing, Germ-Line Mutation/genetics, Humans, Paraganglioma/diagnosis, Pheochromocytoma/diagnosis, Succinate Dehydrogenase/genetics",

author = "{Ben Aim}, Laurene and Maher, {Eamonn R.} and Alberto Cascon and Anne Barlier and Sophie Giraud and Tonino Ercolino and Pascal Pigny and Clifton-Bligh, {Roderick J.} and Delphine Mirebeau-Prunier and Amira Mohamed and Judith Favier and Anne-Paule Gimenez-Roqueplo and Francesca Schiavi and Toledo, {Rodrigo A.} and Dahia, {Patricia L.} and Mercedes Robledo and Nelly Burnichon",

note = "Copyright {\textcopyright} Author(s) (or their employer(s)), 2022. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.",

year = "2022",

month = jul,

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doi = "10.1136/jmedgenet-2020-107652",

language = "English",

volume = "59",

pages = "785--792",

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Ben Aim, L, Maher, ER, Cascon, A, Barlier, A, Giraud, S, Ercolino, T, Pigny, P, Clifton-Bligh, RJ, Mirebeau-Prunier, D, Mohamed, A, Favier, J, Gimenez-Roqueplo, A-P, Schiavi, F, Toledo, RA, Dahia, PL, Robledo, M & Burnichon, N 2022, 'International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma', Journal of Medical Genetics, vol. 59, no. 8, pp. 785-792. https://doi.org/10.1136/jmedgenet-2020-107652

TY - JOUR

T1 - International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma

AU - Ben Aim, Laurene

AU - Maher, Eamonn R.

AU - Cascon, Alberto

AU - Barlier, Anne

AU - Giraud, Sophie

AU - Ercolino, Tonino

AU - Pigny, Pascal

AU - Clifton-Bligh, Roderick J.

AU - Mirebeau-Prunier, Delphine

AU - Mohamed, Amira

AU - Favier, Judith

AU - Gimenez-Roqueplo, Anne-Paule

AU - Schiavi, Francesca

AU - Toledo, Rodrigo A.

AU - Dahia, Patricia L.

AU - Robledo, Mercedes

AU - Burnichon, Nelly

N1 - Copyright © Author(s) (or their employer(s)), 2022. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

PY - 2022/7/21

Y1 - 2022/7/21

N2 - BACKGROUND: SDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the 'NGS and PPGL (NGSnPPGL) Study Group' initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database.METHODS: A total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field.RESULTS: This multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system (https://databases.lovd.nl/shared/genes/SDHB).CONCLUSION: This international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.

AB - BACKGROUND: SDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the 'NGS and PPGL (NGSnPPGL) Study Group' initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database.METHODS: A total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field.RESULTS: This multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system (https://databases.lovd.nl/shared/genes/SDHB).CONCLUSION: This international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.

KW - Adrenal Gland Neoplasms/genetics

KW - Genetic Testing

KW - Germ-Line Mutation/genetics

KW - Humans

KW - Paraganglioma/diagnosis

KW - Pheochromocytoma/diagnosis

KW - Succinate Dehydrogenase/genetics

U2 - 10.1136/jmedgenet-2020-107652

DO - 10.1136/jmedgenet-2020-107652

M3 - Article

C2 - 34452955

SN - 0022-2593

VL - 59

SP - 785

EP - 792

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 8

ER -

International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma

Abstract

Bibliographical note

Keywords

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