Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome.
GAMOS
Galloway-Mowat syndrome
KEOPS complex
proteomic
steroid-resistant nephrotic syndrome
Journal
Frontiers in genetics
ISSN: 1664-8021
Titre abrégé: Front Genet
Pays: Switzerland
ID NLM: 101560621
Informations de publication
Date de publication:
2022
2022
Historique:
received:
31
10
2021
accepted:
16
03
2022
entrez:
11
7
2022
pubmed:
12
7
2022
medline:
12
7
2022
Statut:
epublish
Résumé
Galloway-Mowat syndrome is a rare autosomal recessive disease characterized by a unique combination of renal and neurological manifestations, including early-onset steroid-resistant nephrotic syndrome, microcephaly, psychomotor delay, and gyral abnormalities of the brain. Most patients die during early childhood. Here, we identified a novel homozygous O-sialoglycoprotein endopeptidase (OSGEP) variant, NM_017807.3:c.973C>G (p.Arg325Gly), in four affected individuals in an extended consanguineous family from Saudi Arabia. We have described the detailed clinical characterization, brain imaging results, and muscle biopsy findings. The described phenotype varied from embryonic lethality to early pregnancy loss or death at the age of 9. Renal disease is often the cause of death. Protein modeling of this OSGEP variant confirmed its pathogenicity. In addition, proteomic analysis of the affected patients proposed a link between the KEOPS complex function and human pathology and suggested potential pathogenic mechanisms.
Identifiants
pubmed: 35812735
doi: 10.3389/fgene.2022.806190
pii: 806190
pmc: PMC9259880
doi:
Types de publication
Journal Article
Langues
eng
Pagination
806190Informations de copyright
Copyright © 2022 Ali Alghamdi, Benabdelkamel, Masood, Saheb Sharif-Askari, Hachim, Alsheikh, Hamad, Salih, Bashiri, Alhasan, Kashour, Guatibonza Moreno, Schröder, Karageorgou, Bertoli-Avella, Alkhalidi, Jamjoom, Alorainy, Alfadda and Halwani.
Déclaration de conflit d'intérêts
Authors PGM, SS, VK, and AB-A as employees of CENTOGENE GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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