Dataset Information

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

ABSTRACT: Mutations in the SPATA5-gene are associated with the Epilepsy, Hearing Loss and Mental Retardation Syndrome (EHLMRS). While SPATA5 is ubiquitously expressed and is attributed a role in mitochondrial morphogenesis during spermatogenesis, there is only limited knowledge on the associated muscular and molecular pathology. We report on a case of EHLMRS in an 8-year-old girl with typical clinical presentation, where exome analysis revealed two clinically relevant, compound-heterozygous variants in SPATA5 and a comprehensive workup of muscular pathology was performed including proteomic profiling and microscopic studies. Proteomic profiling of a quadriceps biopsy showed the dysregulation of 82 proteins, out of whom 15 are localized in the mitochondrion, while 19 are associated to diseases presenting with phenotypical overlap to EHLMRS. Histological and immunofluorescence staining of our patient’s muscle biopsy confirmed mitochondrial pathology, while the examination of dysregulated proteins assessed 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Quadriceps

SUBMITTER: Andreas Hentschel

LAB HEAD: Andreas Hentschel

PROVIDER: PXD026182 | Pride | 2022-02-17

REPOSITORIES: Pride

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			Action	DRS
	20201126_142218_NME_Einzel_5rep_62.sne	Other
	20201126_142520_NME_Einzel_5rep_62_Report_2.xls	Xls
	QExactiveHF02_12055_N5790-15_Ctrl1.raw	Raw
	QExactiveHF02_12060_N3591-15_Ctrl2.raw	Raw
	QExactiveHF02_12065_N3446-15_Ctrl3.raw	Raw

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Publications

Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS.

Braun Frederik F Hentschel Andreas A Sickmann Albert A Marteau Theodore T Hertel Swantje S Förster Fabian F Prokisch Holger H Wagner Matias M Wortmann Saskia S Della Marina Adela A Kölbel Heike H Roos Andreas A Schara-Schmidt Ulrike U

International journal of molecular sciences 20210722 15

Mutations in the <i>SPATA5</i> gene are associated with epilepsy, hearing loss and mental retardation syndrome (EHLMRS). While <i>SPATA5</i> 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 ty ...[more]

PMID: 34360601

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