New Term Request: Combined oxidative phosphorylation deficiency 54

[vjenkinsFB]

I'd like to request a term for combined oxidative phosphorylation deficiency 54. The ClinVar listings for this gene are a mess, even ignoring the overlapping read-through product, with multiple things that are actually symptoms rather than syndromes, and might be part of COXPD54. OMIM states that “COXPD54 (619737), which can manifest as Perrault syndrome” (https://www.omim.org/entry/233400) but doesn’t put it in that phenotypic series. It lists all the phenotypes that show up in other places below as part of COXPD54. If you’re not comfortable with making a DOID based on this, just let me know.

OMIM: https://omim.org/entry/619737

Potential definition: Combined oxidative phosphorylation deficiency 54 has_material_basis_in homozygous or compound heterozygous mutation in the PRORP gene on chromosome 14q13.

Potential parent term: combined oxidative phosphorylation deficiency

Synonyms: COXPD54

ClinVar search term: PRORP[gene]

MedGen page(s) pointed to by the above: https://www.ncbi.nlm.nih.gov/medgen/C5676912/ Combined oxidative phosphorylation deficiency 54; https://www.ncbi.nlm.nih.gov/medgen/C4023340/ Childhood onset sensorineural hearing impairment; https://www.ncbi.nlm.nih.gov/medgen/C4551721/ Perrault syndrome 1

MalaCards page: https://www.malacards.org/card/combined_oxidative_phosphorylation_deficiency_54

HGNC entry for gene: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/19958

Citations other than those in the OMIM entry:

• https://pubmed.ncbi.nlm.nih.gov/35663400/ Saoji M, Petersen CE, Sen A, Tripoli BA, Smyth JT, Cox RT. Reduction of Drosophila Mitochondrial RNase P in Skeletal and Heart Muscle Causes Muscle Degeneration, Cardiomyopathy, and Heart Arrhythmia. Front Cell Dev Biol. 2022;10:788516. Published 2022 May 19. doi:10.3389/fcell.2022.788516

FlyBase paper(s) to curate with this term: FBrf0253706

My contact info: vjenkins@morgan.harvard.edu (FlyBase), 0000-0002-1567-7626. Thank you!

[csbjohnson]

Thank you very much for your term request for Combined oxidative phosphorylation deficiency 54, @vjenkinsFB.

We'll review it, get back to you soon and update the DO for the next release.

[lschriml]

Thank you for the new term !! Looking at this Phenotypic series, https://www.omim.org/phenotypicSeries/PS609060?sort=phenotype&order=asc I see we need to add 6 new disease subtypes: combined oxidative phosphorylation deficiency 52-57

Cheers, Lynn

[allenbaron]

Due to the phenotypic variability and possible overlap with Perrault syndrome, I'm going to move target completion for these subtypes to the June release.

[allenbaron]

'combined oxidative phosphorylation deficiency 19' (DOID:0111476) has an Orphanet xref for ORDO:397593 ('Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency') because of defects in LYRM4 (aka ISD11).

@lschriml we should review this xref and perhaps change it to a skos:broadMatch. The other gene linked to that disease in Orphanet is NFS1, which is responsible for 'combined oxidative phosphorylation deficiency 52' (DOID, to be defined; OMIM:619386).

Additional note: The link to OMIM:619386 has not yet been added as an xref on ORDO:397593.

[allenbaron]

'combined oxidative phosphorylation deficiency 54' will be included in the next release as DOID:0070427.

For now, I have chosen to define this disease only by the genetic mutation, due to the variability in phenotype, and not to include any link to Perrault disease since the phenotype only looks like Perrault disease in some patients (sensorineural hearing loss, etc.), while others have no signs or symptoms that overlap with Perrault disease at all.