Miniatura

Fitxers

Bi_allelic_variants.pdf (1.29 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2021-10-01

Llicència de publicació

cc by (c) Hochberg, Irit et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/181732

Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1016/j.ajhg.2021.10.002

Resum

Human mitochondrial RNase P (mt-RNase P) is responsible for 5' end processing of mitochondrial precursor tRNAs, a vital step in mitochondrial RNA maturation, and is comprised of three protein subunits: TRMT10C, SDR5C1 (HSD10), and PRORP. Pathogenic variants in TRMT10C and SDR5C1 are associated with distinct recessive or x-linked infantile onset disorders, resulting from defects in mitochondrial RNA processing. We report four unrelated families with multisystem disease associated with bi-allelic variants in PRORP, the metallonuclease subunit of mt-RNase P. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. Fibroblasts from affected individuals in two families demonstrated decreased steady state levels of PRORP, an accumulation of unprocessed mitochondrial transcripts, and decreased steady state levels of mitochondrial-encoded proteins, which were rescued by introduction of the wild-type PRORP cDNA. In mt-tRNA processing assays performed with recombinant mt-RNase P proteins, the disease-associated variants resulted in diminished mitochondrial tRNA processing. Identification of disease-causing variants in PRORP indicates that pathogenic variants in all three subunits of mt-RNase P can cause mitochondrial dysfunction, each with distinct pleiotropic clinical presentations.

Matèries

Malalties de l'ovari, Malalties rares

Matèries (anglès)

Ovary diseases, Rare diseases

Citació

Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

HOCHBERG, Irit, DEMAIN, Leigh a. m., RICHER, Julie, THOMPSON, Kyle, URQUHART, Jill e., REA, Alessandro, PAGARKAR, Waheeda, RODRÍGUEZ PALMERO, Agustí, SCHLÜTER, Agatha, VERDURA, Edgard, PUJOL, Aurora, QUIJADA FRAILE, Pilar, AMBERGER, Albert, DEUTSCHMANN, Andrea j., DEMETZ, Sandra, GILLESPIE, Meredith, BELYANTSEVA, Inna a., MCMILLAN, Hugh j., BARZIK, Melanie, BEAMAN, Glenda m., MOTHA, Reeya, NG, Kah ying, O’SULLIVAN, James, WILLIAMS, Simon g., BHASKAR, Sanjeev s., LAWRENCE, Isabella r., JENKINSON, Emma m., ZAMBONIN, Jessica l., BLUMENFELD, Zeev, YALONETSKY, Sergey, OERUM, Stephanie, ROSSMANITH, Walter, YUE, Wyatt w., ZSCHOCKE, Johannes, MUNRO, Kevin j., BATTERSBY, Brendan j., FRIEDMAN, Thomas b., TAYLOR, Robert w., O’KEEFE, Raymond t., NEWMAN, William g.. Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations. _The American Journal of Human Genetics_. 2021. Vol. 108, núm. 11, pàgs. 2195-2204. [consulta: 29 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/181732]

Exportar metadades

JSON - METS

Compartir registre