Kyphoscoliosis peptidase deficiency-induced myofibrillar degeneration, focal depletion of mitochondria, and protein aggregation: A true myofibrillar myopathy?
Homozygous <i>KY</i> variants have been described to cause congenital myopathy, myofibrillar myopathy type 7, and hereditary spastic paraplegia. We report the findings in two families harboring the homozygous missense NM_178554.4:c.727T > C p.(Cys243Arg) and splice site NM_178554.4:c.710 + 1G > A <i>KY</i> variants leading to early-onset myopathy with equinovarus deformity, lateral tongue atrophy, kyphoscoliosis, and contractures. Myopathological examination showed a myopathic pattern in conjunction with fibers containing eosinophilic sarcoplasmic inclusions positive for kyphoscoliosis peptidase and filamin-C but not desmin, myofibrillar degeneration, and focal mitochondrial loss. Kyphoscoliosis peptidase protein expression levels were markedly reduced, and <i>in silico</i> analysis of the predicted protein variants suggested impairment of the kyphoscoliosis peptidase catalytic triad.
Authors
- Rolf Schröder (ORCID: https://orcid.org/0000-0002-2772-2615)
- Evren Önay Uçar (ORCID: https://orcid.org/0000-0003-1152-4881)
- Ursula Schlötzer‐Schrehardt (ORCID: https://orcid.org/0000-0001-8423-7395)
- Andreas Hofmann (ORCID: https://orcid.org/0000-0003-4408-5467)
- Christoph S. Clemen (ORCID: https://orcid.org/0000-0002-1291-4219)
- Hacer Durmuş (ORCID: https://orcid.org/0000-0002-6426-676X)
- Caroline A. Sewry (ORCID: https://orcid.org/0000-0003-4870-582X)
- Serdar Ceylaner (ORCID: https://orcid.org/0000-0003-2786-1911)
- Memduh Dursun (ORCID: https://orcid.org/0000-0001-9244-3949)
- Elif Mertoğlu (ORCID: https://orcid.org/0000-0002-3606-4722)
- Yeşim Parman (ORCID: https://orcid.org/0000-0001-9793-6590)
Institutions
- The University of Melbourne (AU)
- University of Cologne (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Great Ormond Street Hospital (GB)
- Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR) (DE)
- Universitätsklinikum Erlangen (DE)
- Salford Royal Hospital (GB)
- Max Rubner Institut (DE)
- Intergen (Turkey) (TR)
- University College London (GB)
- Istanbul University (TR)
Publication Details
- Journal
- Journal of Neuromuscular Diseases
- Published
- 2025-11-12
- DOI
- https://doi.org/10.1177/22143602251387026
- Primary Topic
- Cardiomyopathy and Myosin Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00