Relabel term for BCL10 gene

[mnzelnic]

Mondo term (ID and Label): Immunodeficiency 37 MONDO:0014491

Suggested new label: Combined Immunodeficiency due to BCL10 Deficiency

ORCID ID: 0000-0002-4455-3112

Optional: Any additional information (like supporting evidence, PubMed ID, etc.)

BCL10 was first reported in relation to autosomal recessive combined immunodeficiency in 2014 (Torres et al., PMID: 25365219). Three variants (nonsense and splice donor) that have been reported in 3 probands in 3 publications are included in this curation (PMIDs: 25365219, 32008135, 34868072). The mechanism of pathogenicity appears to be loss of function. Individuals affected with combined immunodeficiency due to BCL10 deficiency present in infancy with severe, recurrent infections. While more evidence is needed to establish the full phenotype, patients reported to date have normal total T cell counts but a deficit of memory T cells combined with impaired effector T cell functions, hypogammaglobulinemia, and decreased memory B cells. Low counts of other T cell subsets and NK cells have been described. Heterozygous carriers are reported as unaffected (PMID: 25365219, 34868072). This gene-disease association is supported by biochemical studies, protein interactions, functional and rescue assays, as well as animal models (PMIDs: 10400625, 24074955, 25365219, 32008135, 11163238, 12910267). BCL10 is a part of the CARD11/9–BCL10–MALT1 (CBM) complex. It acts as a signaling molecule transducing the triggering of cell surface antigen receptors to NF-kappaB activation (PMID: 10400625, 24074955). We have previously established other genes within this complex including CARD11 as definitively associated with severe combined immune deficiency. Affected patient cells show altered NF-kappaB signaling that is rescued by wild type (PMID: 25365219, 32008135). BCL10 knockout mice have B cell lymphopenia, reduced B cell proliferation, hypogammaglobulinemia, and impaired immune responses consistent with combined immunodeficiency (PMID: 11163238, 12910267).

In summary, BCL10 is definitively associated with combined immunodeficiency due to BCL10 deficiency. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen SCID/CID GCEP on the meeting date of December 15, 2022 (SOP Version 9).

@marwa-elnagheeb

[nicolevasilevsky]

In accordance to the Mondo disease naming conventions, we aim to keep the terms from the OMIM series consistent in the branch We can add a synonym and a "ClinGen preferred" tag to this term and I will add your notes above as a comment on the term.

[mnzelnic]

@courtneythaxton

[courtneythaxton]

@nicolevasilevsky

As a follow up to our discussion, would it be possible for you or a Mondo representative to attend some of the SCID GCEP calls to discuss the groups efforts and timeline to update the immunodificiency nomenclature? I believe Michelle (Shelly) has sent a follow email to you to that effect. This group would like to work on the entire immunodificiency phenotypic series and has a desire to use explicit dyadic terms, where appropriate.

Thanks! @courtneythaxton

[nicolevasilevsky]

@courtneythaxton I don't see an email from Shelly. When is this meeting?

[courtneythaxton]

@mnzelnic Would you be able to resend the email to Mondo with your request to meet, or add the meeting times below, thanks!

Courtney

[mnzelnic]

Hi there,

Are you seeing this response?

I have not set up a meeting with the chairs. However, our next meeting is on August 17th at 9AM central time. The following meeting is September 21st at 9AM central time. If these meetings do not work, I can set up something separately with our chairs. What do you think?

Best,

Shelly

Michelle Zelnick, MS, CGC

ClinGen SCID Coordinator

Department of Allergy and Immunology/Neurology

Baylor College of Medicine

(she/her/hers)

[cid:680d2cb7-4c80-4f29-b503-8cb5a09fdd04]​ [cid:a4acd558-baf1-4c7f-9f2e-8f69b3c98b23]

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From: Nicole Vasilevsky @.> Sent: Tuesday, August 8, 2023 12:21 PM To: monarch-initiative/mondo @.> Cc: Zelnick, Michelle N @.>; Author @.> Subject: Re: [monarch-initiative/mondo] Relabel term for BCL10 gene (Issue #6186)

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@courtneythaxtonhttps://urldefense.proofpoint.com/v2/url?u=https-3A__github.com_courtneythaxton&d=DwMCaQ&c=ZQs-KZ8oxEw0p81sqgiaRA&r=DSGQwf5o1VqhrX0ynAfIS3hf9NJwk8N7QEVvVObwWEM&m=dmepO_noA-BRVvy4lgUp_eXwso89AtROEy9KDz-EOfBAhOTI6eVfdiZIKLsLyJoo&s=QCGW5lxzmuYs3YA_wDmJWYgyLPVZpzWsH0sKgK-njU4&e= I don't see an email from Shelly. When is this meeting?

— Reply to this email directly, view it on GitHubhttps://urldefense.proofpoint.com/v2/url?u=https-3A__github.com_monarch-2Dinitiative_mondo_issues_6186-23issuecomment-2D1670015506&d=DwMCaQ&c=ZQs-KZ8oxEw0p81sqgiaRA&r=DSGQwf5o1VqhrX0ynAfIS3hf9NJwk8N7QEVvVObwWEM&m=dmepO_noA-BRVvy4lgUp_eXwso89AtROEy9KDz-EOfBAhOTI6eVfdiZIKLsLyJoo&s=2ovgYrCXkGvQdY_8X7BHXzcKdRaJo5I1js3lm2H8u_4&e=, or unsubscribehttps://urldefense.proofpoint.com/v2/url?u=https-3A__github.com_notifications_unsubscribe-2Dauth_A257AEUPWIHG5LCW2I5MEHDXUJYRBANCNFSM6AAAAAAWZMEQKE&d=DwMCaQ&c=ZQs-KZ8oxEw0p81sqgiaRA&r=DSGQwf5o1VqhrX0ynAfIS3hf9NJwk8N7QEVvVObwWEM&m=dmepO_noA-BRVvy4lgUp_eXwso89AtROEy9KDz-EOfBAhOTI6eVfdiZIKLsLyJoo&s=BujNefZSWAYiRu5F7S3GgNcMKA61xwSf7LN2xv4Wtyo&e=. You are receiving this because you authored the thread.Message ID: @.***>

[nicolevasilevsky]

Hi @mnzelnic, Unfortunately, I am not available at that time, @sabrinatoro can you attend this call on either of those dates?

Otherwise, could you please email me about scheduling a different time?

Thanks! Nicole

[sabrinatoro]

@mnzelnic and @nicolevasilevsky : I also have conflicts. Could we please look for a different day/time? Thank you.

[mnzelnic]

Hi there,

What are your emails? I do not have them.

Best,

Shelly

Michelle Zelnick, MS, CGC

ClinGen SCID Coordinator

Department of Allergy and Immunology/Neurology

Baylor College of Medicine

(she/her/hers)

[cid:63708154-16a6-4497-aa18-97ad1027cc19]​ [cid:2179a750-6cfc-4b5d-9f6b-19f53a3ec8fa]

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From: Sabrina Toro @.> Sent: Tuesday, August 15, 2023 11:31 AM To: monarch-initiative/mondo @.> Cc: Zelnick, Michelle N @.>; Mention @.> Subject: Re: [monarch-initiative/mondo] Relabel term for BCL10 gene (Issue #6186)

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@mnzelnichttps://urldefense.proofpoint.com/v2/url?u=https-3A__github.com_mnzelnic&d=DwMCaQ&c=ZQs-KZ8oxEw0p81sqgiaRA&r=DSGQwf5o1VqhrX0ynAfIS3hf9NJwk8N7QEVvVObwWEM&m=8aLr3ePdBAo-xEVXwkSvlpl9zf58XSnhkdzMObWLA9TEkHRRNgv7-N8pbBKsYC8l&s=-GjQ9ORrSSybEpYp9eyc6jMGquq5R962hicxrrBgrXM&e= and @nicolevasilevskyhttps://urldefense.proofpoint.com/v2/url?u=https-3A__github.com_nicolevasilevsky&d=DwMCaQ&c=ZQs-KZ8oxEw0p81sqgiaRA&r=DSGQwf5o1VqhrX0ynAfIS3hf9NJwk8N7QEVvVObwWEM&m=8aLr3ePdBAo-xEVXwkSvlpl9zf58XSnhkdzMObWLA9TEkHRRNgv7-N8pbBKsYC8l&s=GfGTWTCDf6vB61E1ys8tsilxoyZVf6dAgP5BzUGr7p8&e= : I also have conflicts. Could we please look for a different day/time? Thank you.

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[nicolevasilevsky]

nicole {at} tislab {dot} org sabrina {at} tislab {dot} org

thanks!