PXD018838

PXD018838 is an original dataset announced via ProteomeXchange.

Title	Expanding the phenotype of NUP85 mutations beyond nephrotic syndrome to Primary autosomal recessive microcephaly and Seckel syndrome spectrum disoders
Description	Primary autosomal recessive microcepahly and Seckel syndrome spectrum disodrers (MCPH-SCKS) include a heterogenous group of autosomal recessive inherited diseases characterized by primary (congenital) microcephaly, the absence of visceral abnormalities and a variable degree of cognitive impairment, short stature and facial dysmorphism. Recently, biallelic mutations in the nuclear pore complex (NPC) component nucleoporin 85 gene (NUP85) were reported to cause steroid-resistant nephrotic syndrome (SRNS). Here we report that homozygous mutations in NUP85 can also cause MCPH-SCKS without SRNS and thereby expand the phenotypic spectrum of NUP85-linked diseases. Structural analysis predicts the identified NUP85 mutation to have neither an effect on NPC architecture nor on its interaction with other NUPs. We show that mutant NUP85 is, however, associated with a reduced number of NPCs, abnormal mitotic spindle morphology, altered expression levels of protein involved in of cytoskeletal dynamics and decreased cell viability in patient cells. These altered biological processes can explain the disease-causative nature of the mutant NUP85 associated with the human phenotype. Our results also indicates the link of common cellular mechanism involved in the MCPH-SCKS spectrum disorders and NUP85-associated diseases. In addition to the previous studies, our results broadened the phenotype spectrum of NUP85-specific human disease and emphasizes a role of NUP85 in the development of the nervous system.
HostingRepository	PRIDE
AnnounceDate	2022-08-11
AnnouncementXML	Submission_2022-08-11_08:12:36.384.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carlos Vieira
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-27 21:49:33	ID requested
⏵ 1	2022-08-11 08:12:37	announced

Ravindran E, J, ü, hlen R, Vieira-Vieira CH, Ha T, Salzberg Y, Fichtman B, Luise-Becker L, Martins N, Picker-Minh S, Bessa P, Arts P, Jackson MR, Taranath A, Kamien B, Barnett C, Li N, Tarabykin V, Stoltenburg-Didinger G, Harel A, Selbach M, Dickmanns A, Fahrenkrog B, Hu H, Scott H, Kaindl AM, Expanding the phenotype of NUP85 mutations beyond nephrotic syndrome to primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders. Hum Mol Genet, 30(22):2068-2081(2021) [pubmed]

submitter keyword: Human, primary fibroblasts, NUP85, LC-MSMS

Matthias Selbach
contact affiliation	Max-Delbrück-Centre for Molecular Medicine in the Helmholtz Association
contact email	matthias.selbach@mdc-berlin.de
lab head
Carlos Vieira
contact affiliation	Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft
contact email	carlos.vieira@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018838
     1. Label: PRIDE project
     2. Name: Expanding the phenotype of NUP85 mutations beyond nephrotic syndrome to Primary autosomal recessive microcephaly and Seckel syndrome spectrum disoders