[NTR/TFAP2B]

[elliebroeren]

Preferred gene-related syndrome label
TFAP2B-related PDA and Char syndrome spectrum disorder

Synonyms

Parent term (use OLS, or your favorite ontology browser)
MONDO:0005453

Definition
Any congenital heart disease caused by pathogenic mutations in the TFAP2B gene, which encodes the transcription factor AP-2β. Two overlapping clinical presentations have been associated with TFAP2B mutations; Char syndrome (MIM:169100) and Patent ductus arteriosus 2 (MIM:617035). These phenotypes have been grouped together into one disease entity: TFAP2B - related PDA and Char syndrome spectrum disorder. This disorder is characterized by patent ductus arteriosus, facial dysmorphism and hand anomalies (Orphanet). Additional features include sensorineural hearing loss, scoliosis, dental anomalies, and central diabetes insipidus (PMID: 31012281). Given the spectrum of symptoms associated with this condition, patients may exhibit a combination of these features. The underlying mechanism of the spectrum disorder is both dominant negative and loss-of-function. Pathogenic missense variants reported in Char syndrome patients appear to be dominant negative while loss-of-function alleles in PDA patients are likely to act through haploinsufficiency (GeneReviews).

Definition source
PMID: 31012281

Your nano-attribution (ORCID) or URL for a working group
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[katiermullen]

@elliebroeren Thank you for this new term request!

In reviewing the terms in Mondo, there currently exists the term, MONDO:0008209 'Char syndrome' defined as 'Char syndrome is characterized by the triad of patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies.' From Orphanet:46627.

This term is the child of:

• 'has material basis in germline mutation in' some TFAP2B
• 'multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome'
• 'patent ductus arteriosus'
• 'syndromic disease'

Does this term suit your needs? If so, we can add the synonym 'TFAP2B-related PDA and Char syndrome spectrum disorder' if you could kindly provide your ORCID or another source for this synonym.

Thank you!

[elliebroeren]

Hi Katie, Thank you for your email! The syndromic disorders GCEP had decided to use the name "TFAP2B-related PDA and Char syndrome spectrum disorder" because we wanted to lump the terms, and some patients present with only PDA while others present with the full Char syndrome. Does that work for MONDO, or should we choose a different name? Thank you, Ellie Broeren

…

On Wed, Nov 13, 2024 at 1:39 PM katiermullen ***@***.***> wrote: @elliebroeren <https://github.com/elliebroeren> Thank you for this new term request! In reviewing the terms in Mondo, there currently exists the term, MONDO:0008209 'Char syndrome' defined as 'Char syndrome is characterized by the triad of patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies.' From Orphanet:46627 <https://www.orpha.net/en/disease/detail/46627>. This term is the child of: - 'has material basis in germline mutation in' some TFAP2B - 'multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome' - 'patent ductus arteriosus' - 'syndromic disease' Does this term suit your needs? If so, we can add the synonym 'TFAP2B-related PDA and Char syndrome spectrum disorder' if you could kindly provide your ORCID or another source for this synonym. Thank you! — Reply to this email directly, view it on GitHub <#8256 (comment)>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/A32CJQ2S5MHZCIYWBX4M6MT2AOMEXAVCNFSM6AAAAABQEM4RDGVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDINZUGQ2DGNRXGA> . You are receiving this because you were mentioned.Message ID: ***@***.***>

[katiermullen]

Hi @elliebroeren,

Thank you for your speedy reply!

I am mentioning @sabrinatoro here to make sure she is in agreement.

In Mondo, we would annotate patients with the full Char syndrome using MONDO:0008209 'Char syndrome'. Those patients with only PDA could be classified as having MONDO:0014878 'patent ductus arteriosus 2' that 'has material basis in germline mutation in' some TFAP2B.

Can we have one clin gen term map to two Mondo terms?

[katiermullen]

Update - we need to consider making a pattern for these spectrum disorders.

Could this term be called 'TFAP2B-related congenital heart disease spectrum disorder'?

• Add clin gen label: TFAP2B-related PDA and Char syndrome spectrum disorder
• Def: Any congenital heart disease caused by pathogenic variation(s) in the TFAP2B gene, which encodes the transcription factor AP-2β. This disorder is characterized by patent ductus arteriosus, facial dysmorphism and hand anomalies (Orphanet). Additional features include sensorineural hearing loss, scoliosis, dental anomalies, and central diabetes insipidus (PMID: 31012281). Given the spectrum of symptoms associated with this condition, patients may exhibit a combination of these features. The underlying mechanism of the spectrum disorder is both dominant negative and loss-of-function. Pathogenic missense variants reported in Char syndrome patients appear to be dominant negative while loss-of-function alleles in PDA patients are likely to act through haploinsufficiency (GeneReviews).
• Comment: Two overlapping clinical presentations have been associated with TFAP2B mutations; Char syndrome (MIM:169100) and Patent ductus arteriosus 2 (MIM:617035). These phenotypes have been grouped together into one disease entity: TFAP2B - related PDA and Char syndrome spectrum disorder [Clin Gen].