POLR3A-related Disorders - new parent term

[schmidtj1]

Name: POLR3A-related Disorders

Child Terms:
The following Mondo/ORDO Terms should fall under POLR3A-related Disorders as child terms

• Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome (MONDO:0011897)
• hypomyelinating leukodystrophy 7 (no MondoID; DOID:0060794)
• 4H leukodystrophy (no MondoID; ORDO:289494)
• Tremor-ataxia-central hypomyelination (TACH) syndrome (no MondoID; ORDO:447896)
• Wiedemann-Rautenstrauch syndrome (MONDO:0009910)

Definition: Any disorder in which the cause of disease is due to a variant in the POLR3A gene

[sabrinatoro]

@schmidtj1 Thank you for your request. Please see below some comments

1. I created a new term: "POLR3A-related disorder"
   -child of 'hereditary disease' (MONDO:0003847). Please let me know if you think a more specific parent would be appropriate.
   -Definition: "Disorder in which the cause of disease is a variation in the POLR3A gene.

2. The following requested child should not be a child of "POLR3A-related disorder": 4H leukodystrophy (ORDO:289494)
   This term is also called "POLR-related leukodystrophy". This disease is caused by variation(s) in any of the genes encoding POLR3 (RNA polymerase III) subunits, including POLR3A, POLR3B and POLR1C.
   Therefore this disease is not specific to the POLR3A gene and therefore cannot be made a child of POLR3A-related disorder.

3. The following requested children are already in Mondo:
   -hypomyelinating leukodystrophy 7 (DOID:0060794): MONDO:0011897
   -Tremor-ataxia-central hypomyelination (TACH) syndrome (ORDO:447896): MONDO:0011897

[schmidtj1]

Thanks, Sabrina. When I search in Mondo, I don’t see this come up – is that because it’s not “live” yet? Same for POLR3B and POLR1C which I got notified were completed but I don’t see when I search. Re: the 4H leukodystrophy – indeed, 4H can be caused by multiple genes, but it is still considered at POLR3A-related disorder (also a POLR3B-related disorder, also a POLR1C-related disorder). See here: https://www.ncbi.nlm.nih.gov/books/NBK99167/ When we curate this gene-disease association, we would like to keep the broad description of POLR3A-related disorder because we want to lump 4H in along with the other overlapping phenotype descriptions that are in Mondo/OMIM. So, if we can’t make it a child term, how can we connect it to the Mondo term for POLR3A, POLR3B and POLR1C so that we can include that clinical presentation in our curation? Thanks for any advice! Best, Johanna From: Sabrina Toro ***@***.***> Reply-To: monarch-initiative/mondo ***@***.***> Date: Tuesday, September 17, 2024 at 6:00 PM To: monarch-initiative/mondo ***@***.***> Cc: "Schmidt, Johanna" ***@***.***>, Mention ***@***.***> Subject: [External]Re: [monarch-initiative/mondo] POLR3A-related Disorders - new parent term (Issue #8101) You don't often get email from ***@***.*** Learn why this is important<https://aka.ms/LearnAboutSenderIdentification> @schmidtj1<https://github.com/schmidtj1> Thank you for your request. Please see below some comments 1. I created a new term: "POLR3A-related disorder" -child of 'hereditary disease' (MONDO:0003847). Please let me know if you think a more specific parent would be appropriate. -Definition: "Disorder in which the cause of disease is a variation in the POLR3A gene. 2. The following requested child should not be a child of "POLR3A-related disorder": 4H leukodystrophy (ORDO:289494) This term is also called "POLR-related leukodystrophy". This disease is caused by variation(s) in any of the genes encoding POLR3 (RNA polymerase III) subunits, including POLR3A, POLR3B and POLR1C. Therefore this disease is not specific to the POLR3A gene and therefore cannot be made a child of POLR3A-related disorder. 3. The following requested children are already in Mondo: -hypomyelinating leukodystrophy 7 (DOID:0060794): MONDO:0011897 -Tremor-ataxia-central hypomyelination (TACH) syndrome (ORDO:447896): MONDO:0011897 — Reply to this email directly, view it on GitHub<#8101 (comment)>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/BDU4MILKWDO6MDXGYUUCNB3ZXCRAZAVCNFSM6AAAAABNARZGF2VHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDGNJXGAYTAMJTGM>. You are receiving this because you were mentioned.Message ID: ***@***.***> ** This email originated from an EXTERNAL sender to CHOP. Proceed with caution when replying, opening attachments, or clicking links. Do not disclose your CHOP credentials, employee information, or protected health information to a potential hacker**.

[sabrinatoro]

Hi @schmidtj1 These new terms will be available after the next Mondo release. It is scheduled for October 1st, 2024, and should be available on OLS a few days later.

Regarding 4H leukodystrophy (ORDO:289494) - POLR3-Related Leukodystrophy
I suggest that I create a new term for this term. This term would be a parent term covering leukodystrophy caused by POLR3A, POLR3B and POLR1C.

I want to bring your attention to the fact that this term would be for "leukodystrophy" only, therefore only the leukodystrophies caused by any of the 3 genes above would be under this term.
The terms I created (POLR3A-related disorder, POLR3B-related disorder, POLR1C-related disorder) are for "any disease/disorder" caused by a variation in the gene. If these terms need to be more specific to "leukodystrophies", I can make that change (but I should do it before the October 1st release).

For convenience, here are the questions for which I need answers :-)

1. Are ALL POLR3A-related disorder, POLR3B-related disorder, and POLR1C-related disorder leukodystrophies? (ie are all diseases caused by these genes leukodystrophies)?
2. if some diseases are not leukodystrophies, please list which one are.

Thank you!

Note: this is what the classification would look like (note, to avoid confusion, i would suggest changing the name to POLR3A-related leukodystrophy (same for the POLR3B and POLR1C related disease)

[schmidtj1]

Thank you! I’m going to check in with my colleagues and will get back to you on these questions. Thanks!! Get Outlook for iOS<https://aka.ms/o0ukef>

…

________________________________ From: Sabrina Toro ***@***.***> Sent: Wednesday, September 18, 2024 1:57:04 PM To: monarch-initiative/mondo ***@***.***> Cc: Schmidt, Johanna ***@***.***>; Mention ***@***.***> Subject: [External]Re: [monarch-initiative/mondo] POLR3A-related Disorders - new parent term (Issue #8101) You don't often get email from ***@***.*** Learn why this is important<https://aka.ms/LearnAboutSenderIdentification> Hi @schmidtj1<https://github.com/schmidtj1> These new terms will be available after the next Mondo release. It is scheduled for October 1st, 2024, and should be available on OLS a few days later. Regarding 4H leukodystrophy (ORDO:289494) - POLR3-Related Leukodystrophy I suggest that I create a new term for this term. This term would be a parent term covering leukodystrophy caused by POLR3A, POLR3B and POLR1C. I want to bring your attention to the fact that this term would be for "leukodystrophy" only, therefore only the leukodystrophies caused by any of the 3 genes above would be under this term. The terms I created (POLR3A-related disorder, POLR3B-related disorder, POLR1C-related disorder) are for "any disease/disorder" caused by a variation in the gene. If these terms need to be more specific to "leukodystrophies", I can make that change (but I should do it before the October 1st release). For convenience, here are the questions for which I need answers :-) 1. Are ALL POLR3A-related disorder, POLR3B-related disorder, and POLR1C-related disorder leukodystrophies? (ie are all diseases caused by these genes leukodystrophies)? 2. if some diseases are not leukodystrophies, please list which one are. Thank you! — Reply to this email directly, view it on GitHub<#8101 (comment)>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/BDU4MIKHZF7LLNYOQAW3WX3ZXHEIBAVCNFSM6AAAAABNARZGF2VHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDGNJZGE4TGMRWG4>. You are receiving this because you were mentioned.Message ID: ***@***.***> ** This email originated from an EXTERNAL sender to CHOP. Proceed with caution when replying, opening attachments, or clicking links. Do not disclose your CHOP credentials, employee information, or protected health information to a potential hacker**.

[sabrinatoro]

Hi @schmidtj1
I want to make sure that these terms are correct before they are released to the public, and therefore I am following up on this (though I understand you might still be waiting to hear from your colleagues).

Were the terms you originally requested (POLR3A-related disorder, POLR3B-related disorder, and POLR1C-related disorder) aimed to refer to leukodystrophies? If so, I can update these terms and make them leukodystrophy.

It will be easier to make these terms more general later if needed (and much more complicated to make them more specific).
Thank you !
Sabrina

[schmidtj1]

Hi, Sabrina. Yes, sorry for the delay, I am meeting with my colleagues tomorrow to get you a thorough answer (they are cc’d here). But the short of it is that variants in POLR3A, POLR3B and POLR1C can result in leukodystrophy (for example, 4H leukodystrophy), but do not always. There is a range of phenotypic presentation, which can in some ways be considered a spectrum, thus our desire to curate them as a lumped entity. I think we can better explain it by presenting you with a diagram or something that we can create and send tomorrow if that helps. But bottom line is that we wanted to have all the different phenotype/omim/mondo terms grouped and put under the broad terms of “POLR1A-related disorder, POLR3B-related disorder, and POLR1C-related disorder) so that we can just curate under the one broad term. Does that help for now? Will follow up with you tomorrow! Thanks! Johanna From: Sabrina Toro ***@***.***> Reply-To: monarch-initiative/mondo ***@***.***> Date: Tuesday, September 24, 2024 at 5:50 PM To: monarch-initiative/mondo ***@***.***> Cc: "Schmidt, Johanna" ***@***.***>, Mention ***@***.***> Subject: [External]Re: [monarch-initiative/mondo] POLR3A-related Disorders - new parent term (Issue #8101) Hi @schmidtj1<https://github.com/schmidtj1> I want to make sure that these terms are correct before they are released to the public, and therefore I am following up on this (though I understand you might still be waiting to hear from your colleagues). Were the terms you originally requested (POLR3A-related disorder, POLR3B-related disorder, and POLR1C-related disorder) aimed to refer to leukodystrophies? If so, I can update these terms and make them leukodystrophy. It will be easier to make these terms more general later if needed (and much more complicated to make them more specific). Thank you ! Sabrina — Reply to this email directly, view it on GitHub<#8101 (comment)>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/BDU4MIKAC52MEWFRJZBZAC3ZYHNBHAVCNFSM6AAAAABNARZGF2VHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDGNZSGQ2TANBQGU>. You are receiving this because you were mentioned.Message ID: ***@***.***> ** This email originated from an EXTERNAL sender to CHOP. Proceed with caution when replying, opening attachments, or clicking links. Do not disclose your CHOP credentials, employee information, or protected health information to a potential hacker**.

[sabrinatoro]

Thank you, Johanna.
This is extremely helpful, and I think we already have as you need.

• 'POLR1C-related disorder' (MONDO:0700278): any disorder (leukodystrophy or not) in which the cause of the disease is POLR1C
• 'POLR3B-related disorder' (MONDO:0700277): any disorder (leukodystrophy or not) in which the cause of the disease is POLR3B
• 'POLR3A-related disorder' (MONDO:0700276): any disorder (leukodystrophy or not) in which the cause of the disease is POLR3A

I will reinstate the term: 4H leukodystrophy (ORDO:289494) - POLR3-Related Leukodystrophy
It will be defined as any leukodystrophy caused by POLR3A, POLR3B or POLR1C

Any diseases that are leukodystrophy AND caused by either POLR3A, POLR3B or POLR1C will have 2 ontological parents: (1) 'POLR1C-related disorder' or 'POLR3B-related disorder' or 'POLR3A-related disorder', (2) 'POLR3-Related Leukodystrophy'

[schmidtj1]

That sounds perfect, thank you so much! I’ll still double check with Amy and Julie tomorrow but I think we’re good! Get Outlook for iOS<https://aka.ms/o0ukef>

…

________________________________ From: Sabrina Toro ***@***.***> Sent: Tuesday, September 24, 2024 4:19 PM To: monarch-initiative/mondo ***@***.***> Cc: Schmidt, Johanna ***@***.***>; Mention ***@***.***> Subject: [External]Re: [monarch-initiative/mondo] POLR3A-related Disorders - new parent term (Issue #8101) Thank you, Johanna. This is extremely helpful, and I think we already have as you need. * 'POLR1C-related disorder' (MONDO:0700278): any disorder (leukodystrophy or not) in which the cause of the disease is POLR1C * 'POLR3B-related disorder' (MONDO:0700277): any disorder (leukodystrophy or not) in which the cause of the disease is POLR3B * 'POLR3A-related disorder' (MONDO:0700276): any disorder (leukodystrophy or not) in which the cause of the disease is POLR3A I will reinstate the term: 4H leukodystrophy (ORDO:289494) - POLR3-Related Leukodystrophy It will be defined as any leukodystrophy caused by POLR3A, POLR3B or POLR1C Any diseases that are leukodystrophy AND caused by either POLR3A, POLR3B or POLR1C will have 2 ontological parents: (1) 'POLR1C-related disorder' or 'POLR3B-related disorder' or 'POLR3A-related disorder', (2) 'POLR3-Related Leukodystrophy' — Reply to this email directly, view it on GitHub<#8101 (comment)>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/BDU4MIM5HFTOXHDPHDNFJN3ZYHQM7AVCNFSM6AAAAABNARZGF2VHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDGNZSGQ4DQMBSGE>. You are receiving this because you were mentioned.Message ID: ***@***.***> ** This email originated from an EXTERNAL sender to CHOP. Proceed with caution when replying, opening attachments, or clicking links. Do not disclose your CHOP credentials, employee information, or protected health information to a potential hacker**.