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Braun, F.* ; Hentschel, A.* ; Sickmann, A.* ; Marteau, T.* ; Hertel, S.* ; Förster, F.* ; Prokisch, H. ; Wagner, M. ; Wortmann, S.* ; Della Marina, A.* ; Kölbel, H.* ; Roos, A.* ; Schara‐Schmidt, U.*

Muscular and molecular pathology associated with SPATA5 deficiency in a child with EHLMRS.

Int. J. Mol. Sci. 22:7835 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Mutations in the SPATA5 gene are associated with epilepsy, hearing loss and mental retardation syndrome (EHLMRS). While SPATA5 is ubiquitously expressed and is attributed a role within mitochondrial morphogenesis during spermatogenesis, there is only limited knowledge about the associated muscular and molecular pathology. This study reports on a comprehensive workup of muscular pathology, including proteomic profiling and microscopic studies, performed on an 8‐year‐old girl with typical clinical presentation of EHLMRS, where exome analysis revealed two clinically relevant, compound‐heterozygous variants in SPATA5. Proteomic profiling of a quadriceps biopsy showed the dysregulation of 82 proteins, out of which 15 were localized in the mitochondrion, while 19 were associated with diseases presenting with phenotypical overlap to EHLMRS. Histological staining of our patient’s muscle biopsy hints towards mitochondrial pathology, while the identification of dysregulated proteins attested to the vulnerability of the cell beyond the mitochondria. Through our study we provide insights into the molecular etiology of EHLMRS and provide further evidence for a muscle pathology associated with SPATA5 deficiency, including a pathological histochemical pattern accompanied by dysregulated protein expression.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Ehlmrs ; Mitochondrial Disorder ; Muscle Proteomics ; Myopathology ; Spata5; Trifunctional Protein-deficiency; Mutations; Disorder
ISSN (print) / ISBN 1661-6596
e-ISSN 1422-0067
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 22, Heft: 15, Seiten: , Artikelnummer: 7835 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen European Regional Development Fund (ERDF)
French Muscular Dystrophy Association (AFM-Telethon)
Bundesministerium furBildung und Forschung
European Regional Development Fund
Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen
Bundesministerium für Bildung und Forschung