PXD056347

PXD056347 is an original dataset announced via ProteomeXchange.

Title	Biallelic variants in the mitochondrial ribosomal protein MRPL49 cause combined oxidative phosphorylation deficiency
Description	Combined oxidative phosphorylation deficiency (COXPD) is a rare, multisystem disorder that exhibits significant clinical and genetic heterogeneity. Through genome sequencing, we identified biallelic variants in MRPL49 in individuals from five unrelated families. These individuals presented a spectrum of symptoms, ranging from Perrault syndrome (characterized by primary ovarian insufficiency and sensorineural hearing loss) to severe childhood-onset conditions such as developmental delay, leukodystrophy, microcephaly, and retinal dystrophy. Multiple assays demonstrated that the disease-associated MRPL49 variants disrupted the stability and function of the mitochondrial ribosome, particularly affecting the large subunit. This disruption led to a reduction in Complex I and Complex IV levels. We describe a new form of MRPL49 variant-associated COXPD, thereby expanding the understanding of how impaired assembly of the mitochondrial ribosomal large subunit results in multisystem phenotypes.
HostingRepository	PRIDE
AnnounceDate	2025-03-05
AnnouncementXML	Submission_2025-03-04_18:28:17.158.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD056347
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alfredo Cabrera-Orefice
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-28 19:47:43	ID requested
⏵ 1	2025-03-04 18:28:17	announced

10.1016/J.AJHG.2025.02.005;

10.6019/PXD056347;

submitter keyword: Perrault syndrome, rare disease, mitochondrial large ribosomal subunit,MRPL49, mitoribosome, combined oxidative phosphorylation deficiency

Ilka Wittig
contact affiliation	Centre for Functional Proteomics, Medical Faculty, Goethe University, Frankfurt am Main, Germany.
contact email	wittig@med.uni-frankfurt.de
lab head
Alfredo Cabrera-Orefice
contact affiliation	Goethe University Frankfurt
contact email	alfredbiomed@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056347
     1. Label: PRIDE project
     2. Name: Biallelic variants in the mitochondrial ribosomal protein MRPL49 cause combined oxidative phosphorylation deficiency