Multiple monogenic benign skin tumours
Gene: PRDM10
Comment on gene rating: This gene should be rated RED as it has only been identified with a variant in this gene from one family.
PMID:36440963 reported a family presenting with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with Birt-Hogg-Dubé syndrome (BHD, MIM #135150) based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. A heterozygous missense variant (p.Cys677Tyr) was identified, which co-segregated with the phenotype in the family.
Functional studies show that Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN.
This gene has not yet been associated with phenotypes either in OMIM or in Gene2Phenotype.
Sources: LiteratureCreated: 27 Mar 2023, 11:55 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086
Publications
gene: PRDM10 was added gene: PRDM10 was added to Multiple monogenic benign skin tumours. Sources: Literature Mode of inheritance for gene: PRDM10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRDM10 were set to 36440963 Phenotypes for gene: PRDM10 were set to Fibrofolliculoma, HP:0030436; lipomatosis, MONDO:0006574; renal cell carcinoma, MONDO:0005086 Review for gene: PRDM10 was set to RED