New Term Request: Parkinson’s disease 25

[vjenkinsFB]

I'd like to request a term for Parkinson’s disease 25.

OMIM: https://www.omim.org/entry/620482

Potential definition: Parkinson’s disease 25 is an early-onset Parkinson’s disease that has_material_basis_in the PTPA gene on chromosome 9q34.

Potential parent term: early-onset Parkinson's disease

Synonyms: Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development; PD25

ClinVar search term: (ptpa[gene] AND (1[VARLEN]:1000[VARLEN] AND "single gene"[Properties]))

MedGen page(s) pointed to by the above: https://www.ncbi.nlm.nih.gov/medgen/CN372710/

HGNC entry for gene: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9308

Citations other than those in the OMIM entry (first two are direct responses to the paper establishing PD25):

• Dulski J, Soto-Beasley AI, Uitti RJ, Wszolek ZK, Ross OA. PTPA variants are rare in early-onset and familial Parkinson's disease [published online ahead of print, 2023 Jul 14]. Brain. 2023;awad244. doi:10.1093/brain/awad244
• Ostrožovičová M, Mecheri Y, Al-Mubarak BR, et al. PTPA variants and the risk for Parkinson's disease in diverse ancestry populations [published online ahead of print, 2023 Jul 19]. Brain. 2023;awad247. doi:10.1093/brain/awad247
• Li C, Lin J, Jiang Q, et al. Cross-Ethnic Variant Screening and Burden Analysis of PTPA in Parkinson's Disease. Mov Disord. 2023;38(6):1099-1104. doi:10.1002/mds.29411

FlyBase paper(s) to curate with this term: FBrf0256308

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

[lschriml]

Thank you for the new term, we will get it added shortly. Cheers, Lynn

[allenbaron]

Just a few notes:

• Identified homozygous mutations in PD are very rare.
• I've included it but I'm not convinced that the compound heterozygous portion of the inheritance is merited since all the patients with the described phenotype have homozygous mutations (only 5 total: 4 described in the original publication by Fevga et al and 1 by Li et al).
• The patient described by Li et al was above the DO's cutoff for juvenile PD, so this has been classified only under early-onset.
• There are are some PD patients with compound heterozygous mutations in PTPA but none were noted as having intellectual disability and the great majority would not be considered early-onset. Those that would be considered "early-onset" based on DO's definition (DOID:0060894) are in their 40s, about 2 decades older than these patients.
• Some patients with PD have heterozygous mutations in PTPA. They tend to be older, fitting the "late-onset" definition of the DO (DOID:0060892) in most cases.

Fevga, C., Tesson, C., Carreras Mascaro, A., Courtin, T., van Coller, R., Sakka, S., Ferraro, F., Farhat, N., Bardien, S., Damak, M., Carr, J., Ferrien, M., and 16 others. PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability. Brain 146: 1496-1510, 2023. PubMed: 36073231