PXD036407-1

PXD036407 is an original dataset announced via ProteomeXchange.

Title	Bi-allelic variants of FILIP1 cause a congenital syndrome defined by facial dysmorphisms and a broad range of neurological manifestations
Description	Filamin-A-interacting protein 1 (FILIP1) is a structural protein known to take on roles in neuronal and muscle function and integrity and to interact in addition to filamin-A with filamin-C. For both proteins pathogenic variants in the corresponding genes were linked to neurological symptoms and dysmorphisms (FLNA) or muscular diseases (FLNC) characterized by myofibrillar perturbations. Here, we report on five patients from four unrelated consanguineous families with homozygous FILIP1 variants (two nonsense and two missense) leading to a broad spectrum of neurological symptoms including brain malformations, neurodevelopmental delay as well as muscle weakness and pathology complicated by dysmorphic features shared among patients. Microscopic studies on the muscle biopsy derived from one patient harbouring a missense variant revealed core-like zones of myofibrillar disintegration, autophagic vacuoles and accumulation of FLNc thus introducing FILIP1 as a novel candidate gene of myofibrillar myopathies. Further functional studies confirmed the altered stability of this p.[Pro1133Leu] missense-mutant FILIP1 protein. Proteomic studies on the fibroblasts derived from the same patient revealed a dysregulation of a variety of proteins including FLNc, a biochemical finding which might accord with the manifestation of certain symptoms associated with the syndromic phenotype of FILIP1opathy.
HostingRepository	PRIDE
AnnounceDate	2024-05-23
AnnouncementXML	Submission_2024-05-23_00:56:51.806.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Hentschel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-30 14:24:37	ID requested
⏵ 1	2024-05-23 00:56:52	announced

10.1093/brain/awad152;

Roos A, van der Ven PFM, Alrohaif H, K, ö, lbel H, Heil L, Della Marina A, Weis J, A, ß, ent M, Beck-W, ö, dl S, Barresi R, T, ö, pf A, O'Connor K, Sickmann A, Kohlschmidt N, El Gizouli M, Meyer N, Daya N, Grande V, Bois K, Kaiser FJ, Vorgerd M, Schr, ö, der C, Schara-Schmidt U, Gangfuss A, Evangelista T, R, ö, bisch L, Hentschel A, Gr, ü, neboom A, Fuerst DO, Kuechler A, Tzschach A, Depienne C, Lochm, ü, ller H, Bi-allelic variants of FILIP1 cause congenital myopathy, dysmorphism and neurological defects. Brain, 146(10):4200-4216(2023) [pubmed]

submitter keyword: vacuolar myopathy, protein aggregate myopathy, FLNC, FLNA,MFM/ myofibrillar myopathy

Dr. Andreas Hentschel
contact affiliation	Proteomics, Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Germany
contact email	andreas.hentschel@isas.de
lab head
Andreas Hentschel
contact affiliation	Leibniz Institut für Analytische Wissenschaften
contact email	andreas.hentschel@isas.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD036407

PRIDE project URI

• PRIDE
  1. PXD036407
     1. Label: PRIDE project
     2. Name: Bi-allelic variants of FILIP1 cause a congenital syndrome defined by facial dysmorphisms and a broad range of neurological manifestations