Multiminicore Disease (MmD) — Comprehensive Disease Characteristics Report

Scope note. “Multiminicore disease” is a muscle-biopsy-defined congenital myopathy phenotype characterized by multiple “core-like” lesions (“minicores”) and is genetically heterogeneous; in practice, many modern sources treat classic MmD largely within the spectrum of SELENON (SEPN1)-related myopathy and RYR1-related myopathies. Evidence below therefore covers MmD as a clinicopathologic entity and highlights the two best-supported genetic subtypes. (lillis2012clinicalutilitygene pages 1-2, jungbluth2007multiminicoredisease pages 1-2)

1. Disease Information

1.1 Definition and current understanding

Multiminicore disease (MmD) is an inherited congenital myopathy defined by the presence of multiple “minicores” on skeletal muscle biopsy. Minicores are “multifocal, well-circumscribed areas” with reduced oxidative staining that “extend only for a short distance along the longitudinal axis of the muscle,” and on electron microscopy show “myofibrillar disruption and paucity of mitochondria.” (jungbluth2007multiminicoredisease pages 5-7)

The “classic” MmD phenotype is commonly described by the clinical triad of axial weakness, spinal rigidity/early scoliosis, and respiratory impairment (often disproportionate to limb weakness). (jungbluth2007multiminicoredisease pages 2-3, jungbluth2007multiminicoredisease pages 1-2)

1.2 Key identifiers (available from retrieved evidence)

• OMIM / MIM disease IDs mentioned in retrieved evidence: MmD (MIM #255320); additional MmD-related OMIM numbers listed in a clinical utility gene card: #117000 and #607552. (lillis2012clinicalutilitygene pages 1-2, zorzato2007functionaleffectsof pages 1-3)
• Gene OMIM IDs mentioned in retrieved evidence:
• RYR1 (*180901) (lillis2012clinicalutilitygene pages 1-2)
• SEPN1 / SELENON (*606210) (lillis2012clinicalutilitygene pages 1-2, zorzato2007functionaleffectsof pages 1-3)

Not found in the retrieved sources: MONDO ID, ICD-10/ICD-11 codes, MeSH term IDs, and Orphanet ORPHA identifiers were not explicitly present in the accessible full text excerpts; therefore they cannot be cited here. (jungbluth2007multiminicoredisease pages 1-2, lillis2012clinicalutilitygene pages 1-2)

1.3 Synonyms / alternative names

Synonyms reported include minicore myopathy, multicore myopathy, and minicore myopathy with external ophthalmoplegia (a recognized clinical presentation particularly in RYR1-related disease). (jungbluth2007multiminicoredisease pages 1-2)

1.4 Evidence source type

The information summarized here is derived from aggregated disease-level resources (reviews/gene cards) and aggregated cohorts (international and national observational studies), rather than EHR-only single-center data. (jungbluth2007multiminicoredisease pages 1-2, villarquiles2020theclinicalhistologic pages 1-2, bouman2023selenonrelatedmyopathyacross pages 1-3)

2. Etiology

2.1 Primary causal factors

MmD is primarily a genetic disorder (Mendelian), with major subtypes: - SELENON (SEPN1)-related MmD / SELENON-related myopathy: classically associated with a consistent phenotype including early spinal rigidity/scoliosis and prominent respiratory involvement. (lillis2012clinicalutilitygene pages 1-2, jungbluth2007multiminicoredisease pages 2-3) - RYR1-related MmD: phenotypically broader; ophthalmoparesis/external ophthalmoplegia is common; malignant hyperthermia risk is an anesthetic consideration in RYR1-associated disease. (lillis2012clinicalutilitygene pages 1-2, jungbluth2007multiminicoredisease pages 2-3)

2.2 Risk factors

• Genetic risk is driven by biallelic pathogenic variants in causal genes (most often SELENON/SEPN1 for the classic rigid-spine/respiratory phenotype, and RYR1 for other multicore/minicore phenotypes). (jungbluth2007multiminicoredisease pages 2-3, zorzato2007functionaleffectsof pages 1-3)
• In the largest SEPN1/SELENON cohort (n=132), bi-allelic null mutations were associated with higher disease severity (p=0.017). (villarquiles2020theclinicalhistologic pages 1-2)

Environmental risk factors: no specific toxin/lifestyle exposures were identified as causes in the retrieved primary sources. However, clinical deterioration can be influenced by management-related factors (e.g., untreated nocturnal hypoventilation and scoliosis progression), which act as modifiable determinants of severity. (villarquiles2020theclinicalhistologic pages 1-2, villarquiles2020theclinicalhistologic pages 4-5)

2.3 Protective factors and gene–environment interactions

No specific protective variants or validated environmental protective factors were identified in the retrieved evidence for MmD itself. (villarquiles2020theclinicalhistologic pages 1-2)

3. Phenotypes

3.1 Core phenotype set (classic MmD)

Key phenotype domains (with HPO term suggestions): - Axial muscle weakness (HP:0003323 Axial muscle weakness; also HP:0003798 Neck flexor weakness) (jungbluth2007multiminicoredisease pages 2-3, jungbluth2007multiminicoredisease pages 1-2) - Spinal rigidity / rigid spine (HP:0003301 Rigid spine) (villarquiles2020theclinicalhistologic pages 4-5) - Scoliosis (HP:0002650 Scoliosis) (villarquiles2020theclinicalhistologic pages 4-5) - Respiratory insufficiency / hypoventilation, often nocturnal first (HP:0002093 Respiratory insufficiency; HP:0002872 Sleep-related hypoventilation) (villarquiles2020theclinicalhistologic pages 4-5) - Ophthalmoparesis/external ophthalmoplegia in RYR1-related MmD subgroups (HP:0000602 Ophthalmoplegia) (lillis2012clinicalutilitygene pages 1-2, jungbluth2007multiminicoredisease pages 1-2)

3.2 Phenotype frequencies and timing (SELENON/SEPN1 cohort)

In a large international retrospective cohort of 132 individuals with SEPN1/SELENON-related myopathy (age 2–58 years) followed for decades: - Scoliosis occurred in 86.1% (mean onset 8.9 ± 4 years). (villarquiles2020theclinicalhistologic pages 1-2) - Respiratory failure developed in 100% (mean onset 10.1 ± 6 years). (villarquiles2020theclinicalhistologic pages 1-2) - Assisted ventilation was required in 81.9%, often while still ambulant. (villarquiles2020theclinicalhistologic pages 4-5) - Rigid spine was common (~87.8% in one excerpted analysis). (villarquiles2020theclinicalhistologic pages 3-4) - Muscle biopsy: multi-minicores were the most common lesion (59.5%), with variable additional features (mild dystrophic changes; Mallory-like eosinophilic inclusions in 6.3%). (villarquiles2020theclinicalhistologic pages 1-2, villarquiles2020theclinicalhistologic pages 5-7)

Disease severity in this cohort was classified as severe 28.4%, moderate 53.1%, and mild 18.5% (subset with detailed phenotyping). (villarquiles2020theclinicalhistologic pages 7-8)

3.3 Quality of life and symptom burden (recent quantitative data)

A Dutch cross-sectional “trial readiness” study of 11 genetically confirmed SELENON-RM patients (mean age 20±13 years; range 3–42) reported: - Mean MFM-20/32 total score 71.2 ± 15.1% (domain 1—standing/transfers—most affected). (bouman2023selenonrelatedmyopathyacross pages 1-3) - Problematic fatigue, pain, and impaired quality of life were prominent in patient-reported outcomes. (bouman2023selenonrelatedmyopathyacross pages 1-3, bouman2023selenonrelatedmyopathyacross pages 14-16) - Respiratory impairment in all patients with marked diaphragm dysfunction regardless of age. (bouman2023selenonrelatedmyopathyacross pages 1-3)

3.4 Suggested anatomical structures affected (UBERON) and cell types (CL)

• Primary tissue: skeletal muscle (UBERON:0001134). (jungbluth2007multiminicoredisease pages 5-7)
• Respiratory muscle involvement, especially diaphragm (UBERON:0001103), is a major determinant of morbidity. (bouman2023selenonrelatedmyopathyacross pages 10-13)
• Relevant cell type emphasis for mechanism mapping: skeletal muscle fiber / myofiber (CL:0000187) and skeletal muscle satellite cell (CL:0000516; supported indirectly by SelN roles in muscle biology and disease mechanisms). (castets2012selenoproteinnin pages 7-8)

4. Genetic / Molecular Information

4.1 Causal genes (best-supported)

• SELENON (SEPN1): autosomal recessive; classically associated with the rigid spine–scoliosis–respiratory phenotype of MmD/SELENON-related myopathy. (lillis2012clinicalutilitygene pages 1-2, villarquiles2020theclinicalhistologic pages 1-2)
• RYR1: autosomal dominant or recessive across the RYR1-related myopathy spectrum; recessive forms commonly underlie MmD presentations and may overlap with central core disease. (jungbluth2007multiminicoredisease pages 2-3, todd2024rycals48168(arm210) pages 1-2)

4.2 Pathogenic variant spectrum and genotype–phenotype

In the SEPN1/SELENON international cohort (n=132), 65 SEPN1 mutations were identified (32 novel), including the first pathogenic copy-number variant, with exon 1 as a mutational hotspot; bi-allelic null variants correlated with greater severity. (villarquiles2020theclinicalhistologic pages 1-2)

4.3 Molecular functions (current mechanistic consensus)

• SELENON/SelN is an ER/SR-localized, redox-active selenoprotein implicated in regulating oxidative stress and calcium handling, including interaction with ryanodine receptors; SelN deficiency increases oxidative stress in patient cells and reduces RyR function in biochemical assays. (castets2012selenoproteinnin pages 7-8)
• SEPN1/SELENON is also described as an ER Ca2+-linked redox regulator that can activate SERCA in a redox-dependent manner (mechanistic model discussed in a 2024 thesis-derived excerpt). (germani2024chopero1apathwayof pages 17-21)

5. Environmental Information

No specific infectious triggers or environmental toxic exposures are implicated as primary causes in the retrieved literature. The clinically most relevant “environmental” aspects are perioperative/anesthetic exposures in RYR1-related disease because of malignant hyperthermia susceptibility; anesthetic precautions are recommended in RYR1-associated cases. (jungbluth2007multiminicoredisease pages 2-3)

6. Mechanism / Pathophysiology

6.1 Causal chain (SELENON/SEPN1-related)

A synthesis from mechanistic and translational studies supports this chain: 1. SELENON loss-of-function → dysregulated ER/SR redox and stress responses and impaired regulation of calcium-handling proteins (RyR and SERCA). (castets2012selenoproteinnin pages 7-8, germani2024chopero1apathwayof pages 17-21) 2. Increased ER stress and maladaptive UPR signaling can involve the CHOP/ERO1A axis, with ERO1A upregulation observed in SEPN1-RM models and patient biopsies. (germani2024sepn1relatedmyopathydepends pages 1-3, germani2024chopero1apathwayof pages 68-72) 3. Downstream consequences include impaired ER–mitochondria functional coupling and mitochondrial bioenergetics defects, contributing to muscle weakness and vulnerability of respiratory muscles (especially diaphragm). (germani2024sepn1relatedmyopathydepends pages 1-3, bouman2023selenonrelatedmyopathyacross pages 10-13)

6.2 Key 2024 development: ERO1A as a target and TUDCA as a candidate therapy

A 2024 Cell Reports Medicine study identified ERO1A as a disease-relevant factor in SEPN1-related myopathy and reported both genetic and pharmacologic rescue: - ERO1A depletion/knockout in SEPN1-loss contexts reduced ER stress and rescued Ca2+ handling and mitochondrial bioenergetics, reversing diaphragmatic weakness in mice. (germani2024sepn1relatedmyopathydepends pages 1-3) - Treatment with TUDCA (tauroursodeoxycholic acid), described as an ER-stress inhibitor/chemical chaperone, mirrored aspects of ERO1A-loss rescue in SEPN1 KO mice and improved bioenergetics in patient-derived myoblasts. (germani2024sepn1relatedmyopathydepends pages 1-3)

Ontology mapping suggestions (mechanism): - ER stress / unfolded protein response: GO:0030968 (endoplasmic reticulum unfolded protein response) - Oxidation–reduction / oxidative stress: GO:0055114 (oxidation-reduction process), GO:0006979 (response to oxidative stress) - Calcium ion homeostasis: GO:0055074 (calcium ion homeostasis) - Mitochondrial bioenergetics: GO:0006119 (oxidative phosphorylation)

6.3 RYR1-related MmD mechanisms

RYR1-related myopathies involve dysfunction of the skeletal muscle SR Ca2+ release channel central to excitation–contraction coupling. Reported pathophysiologic contributors include SR Ca2+ leak and altered channel regulation (e.g., reduced calstabin1 association, oxidative stress, altered open probability), providing a rationale for RyR1-stabilizing compounds (Rycals). (todd2024rycals48168(arm210) pages 1-2)

7. Anatomical Structures Affected

• Primary organ/system: skeletal muscle (UBERON:0001134). (jungbluth2007multiminicoredisease pages 5-7)
• Clinically dominant functional vulnerability: respiratory pump muscles, particularly the diaphragm (UBERON:0001103), reflected by severe reductions in forced vital capacity and large sitting-to-supine VC drops in SELENON-RM patients. (bouman2023selenonrelatedmyopathyacross pages 10-13)
• Musculoskeletal system: spine with rigid spine phenotype and scoliosis; scoliosis frequently requires stabilization surgery in adolescence in SELENON-RM. (villarquiles2020theclinicalhistologic pages 5-7)

8. Temporal Development

8.1 Onset

In the SEPN1/SELENON cohort, first signs occurred within the first 2 years in 84.7% (mean ~18 months), though presentations can vary. (villarquiles2020theclinicalhistologic pages 3-4)

8.2 Progression

SEPN1/SELENON-related myopathy is often considered slowly progressive but the large cohort emphasized it can be “more severe and progressive than previously thought,” with systematic functional decline from the end of the third decade, loss of ambulation in ~10%, and reduced lifespan even in mild cases. (villarquiles2020theclinicalhistologic pages 1-2)

9. Inheritance and Population

9.1 Inheritance

• Classic MmD subtypes are commonly autosomal recessive, particularly SELENON/SEPN1-related disease; RYR1-related disease may be autosomal dominant or recessive depending on phenotype. (jungbluth2007multiminicoredisease pages 2-3, todd2024rycals48168(arm210) pages 1-2)

9.2 Epidemiology

• An incidence estimate reported in a 2024 thesis excerpt: ~1.03 per million in France (country-specific; likely dependent on ascertainment and definitions). (germani2024chopero1apathwayof pages 17-21)

9.3 Prognostic factors and population modifiers

In the SEPN1/SELENON cohort, major determinants of severity/prognosis included scoliosis/respiratory management, SEPN1 genotype (including null variants), and body mass abnormalities. (villarquiles2020theclinicalhistologic pages 1-2)

10. Diagnostics

10.1 Clinical diagnostic concept

Clinical suspicion is raised by the classic triad (axial weakness + rigid spine/scoliosis + respiratory involvement) and confirmed by either: - Muscle biopsy demonstrating predominant minicores; and/or - Genetic confirmation of causal variants (increasingly the dominant approach). (jungbluth2007multiminicoredisease pages 5-7, lillis2012clinicalutilitygene pages 1-2)

10.2 Biopsy (histopathology)

• Minicores: reduced oxidative staining lesions short along the fiber axis, with mitochondrial paucity and sarcomeric disruption. (jungbluth2007multiminicoredisease pages 5-7)
• SELENON-related MmD: often numerous small, poorly defined minicores distributed throughout fibers. (lillis2012clinicalutilitygene pages 1-2)

10.3 Imaging and real-world implementation

Muscle MRI can support subtype discrimination and guide genetic testing; an Orphanet review provides MRI patterns and a subtype comparison table (images retrieved). (jungbluth2007multiminicoredisease media eac91681, jungbluth2007multiminicoredisease media f3b69ea4)

10.4 Respiratory testing

Because respiratory impairment can be disproportionate and may manifest first as nocturnal hypoventilation, polysomnography and upright/supine spirometry are clinically important; in the SEPN1/SELENON cohort, nocturnal hypoventilation was detected by polysomnography in 92.9%. (villarquiles2020theclinicalhistologic pages 4-5)

10.5 Differential diagnosis (evidence-supported highlights)

• Other congenital myopathies with cores/minicores, including broader RYR1-related phenotypes and other genetically distinct congenital myopathies where multicore pathology can occur. (jungbluth2007multiminicoredisease pages 2-3, butterfield2019congenitalmusculardystrophy pages 14-15)

11. Outcomes / Prognosis

From the international SEPN1/SELENON cohort (n=132): - Respiratory failure is universal and a major determinant of prognosis; assisted ventilation was required in ~82% and often while ambulant. (villarquiles2020theclinicalhistologic pages 1-2, villarquiles2020theclinicalhistologic pages 4-5) - Disease can be progressive with adulthood decline and reduced lifespan even in milder phenotypes. (villarquiles2020theclinicalhistologic pages 1-2)

From the Dutch cross-sectional study (n=11), additional clinically actionable morbidity signals include: - High prevalence of low bone mineral density (80%) and fragility long-bone fractures (55%). (bouman2023selenonrelatedmyopathyacross pages 1-3) - Subclinical cardiac abnormalities (abnormal global longitudinal strain in 43% and QRS fragmentation in 80%), despite preserved LVEF. (bouman2023selenonrelatedmyopathyacross pages 1-3)

12. Treatment

12.1 Current standard of care (supportive)

Evidence from cohort studies supports multi-domain supportive management: - Respiratory care: routine respiratory monitoring; many patients require nocturnal non-invasive ventilation; diaphragm dysfunction is common across ages in SELENON-RM. (villarquiles2020theclinicalhistologic pages 4-5, bouman2023selenonrelatedmyopathyacross pages 10-13) - Orthopedic/spine management: scoliosis is frequent and often progressive; spinal arthrodesis is commonly performed in adolescence and stabilizes scoliosis. (villarquiles2020theclinicalhistologic pages 5-7) - Bone health: vitamin D supplementation and calcium intake optimization recommended due to frequent low BMD and fractures. (bouman2023selenonrelatedmyopathyacross pages 1-3, bouman2023selenonrelatedmyopathyacross pages 13-14) - Symptom management: interventions targeting fatigue and pain, including rehabilitation/physical therapy and self-management approaches, were recommended in the Dutch cohort study. (bouman2023selenonrelatedmyopathyacross pages 13-14, bouman2023selenonrelatedmyopathyacross pages 14-16)

Suggested MAXO terms (treatment actions): - Noninvasive ventilation (MAXO:0000502 noninvasive ventilation) - Respiratory function monitoring (MAXO:0000470 respiratory function monitoring) - Physical therapy (MAXO:0000019 physical therapy) - Vitamin D supplementation (MAXO:0000752 vitamin D supplementation) - Calcium supplementation (MAXO:0000751 calcium supplementation)

12.2 Experimental / emerging therapeutics (2023–2024 priority)

A. TUDCA targeting ER stress in SEPN1/SELENON-related myopathy (2024) A translational mouse + patient-cell study suggests TUDCA may mitigate downstream ER-stress/bioenergetic defects and improve diaphragm weakness in SEPN1 deficiency models, nominating an actionable pathway (ERO1A/ER stress) and candidate therapy. (germani2024sepn1relatedmyopathydepends pages 1-3)

B. ARM210 (Rycal S48168) in RYR1-related myopathies (Phase 1, 2024) A phase 1, open-label, dose-escalation study (NCT04141670) reported ARM210 was well tolerated over 29 days and exploratory measures suggested improvements in fatigue and proximal strength in most participants at the 200 mg dose, supporting randomized proof-of-concept testing. (todd2024rycals48168(arm210) pages 1-2)

C. Gene editing proof-of-concept for RYR1 (Prime editing; 2023) Prime editing was used to correct a recessive RYR1 point mutation (T4709M) in human myoblasts with a reported 59% correction rate, demonstrating feasibility of precise editing strategies for RYR1-related myopathies. (godbout2023successfulcorrectionby pages 1-3)

13. Prevention

Primary prevention is not currently feasible for genetically determined MmD. Prevention in practice focuses on: - Genetic counseling and cascade testing after molecular diagnosis (implied by the strong autosomal recessive inheritance and genetic test-centric diagnosis). (villarquiles2020theclinicalhistologic pages 1-2) - Tertiary prevention of complications through proactive management of respiratory insufficiency, scoliosis, and bone health. (villarquiles2020theclinicalhistologic pages 4-5, bouman2023selenonrelatedmyopathyacross pages 13-14)

14. Other Species / Natural Disease

Evidence in the retrieved sources supports cross-species relevance primarily through experimental modeling: SelN/SELENON deficiency phenotypes have been reproduced in zebrafish (muscle disorganization resembling human multiminicore disease), supporting evolutionary conservation of key muscle pathways. (bellinger2009regulationandfunction pages 2-4)

15. Model Organisms

• Mouse (SEPN1 KO) models: used to identify the ERO1A dependency and demonstrate pharmacologic rescue with TUDCA; diaphragm weakness was a key functional endpoint in vivo. (germani2024sepn1relatedmyopathydepends pages 1-3)
• Mouse (RYR1 I4895T) models: described as developing core/minicore pathology and used to study UPR/ER-stress pathway involvement and modifiers (in thesis-derived mechanistic summary). (germani2024chopero1apathwayof pages 17-21, germani2024chopero1apathwayof pages 68-72)
• Zebrafish SELENON knockdown: reported muscle fiber disorganization resembling human multiminicore disease. (bellinger2009regulationandfunction pages 2-4)

Recent developments and real-world implementations (2023–2024 emphasis)

Trial-readiness and outcome measures in clinical care

• Quantitative endpoints and monitoring: MFM-20/32, accelerometry, and muscle ultrasound were proposed as feasible measures for clinical trials and potentially for structured clinical follow-up in SELENON-RM. (bouman2023selenonrelatedmyopathyacross pages 1-3)
• Cardiac and bone surveillance: The Dutch cross-sectional cohort recommended routine cardiorespiratory follow-up and emphasized the burden of low BMD and subtle cardiac abnormalities (GLS/QRS fragmentation), informing real-world multidisciplinary care. (bouman2023selenonrelatedmyopathyacross pages 1-3, bouman2023selenonrelatedmyopathyacross pages 13-14)

Key ongoing or recent studies (ClinicalTrials.gov)

• NCT06157268 (READYCOM) — Natural history + fatigability study in congenital myopathies including MmD/CCD (Radboud UMC). Observational; recruiting; start 2024-03-28; primary outcome: MFM change over 24 months; includes endurance shuttle test for fatigability. (NCT06157268 chunk 1)
• NCT04478981 (LAST STRONG) — Natural history of SELENON(SEPN1) or LAMA2 disease (Radboud UMC). Observational; completed; n=38; repeated assessments over 1.5 years; primary outcome: MFM change. (NCT04478981 chunk 1)
• NCT00272883 — Boston Children’s Hospital congenital myopathy genetics and phenotyping program; observational; recruiting; target enrollment 4000; includes SELENON and RYR1 myopathy including MmD. (NCT00272883 chunk 1)
• NCT06791369 — Prevalence of RYR1-related disease; observational; not yet recruiting; planned start 2025; aims to estimate prevalence and subgroup frequencies (including MmD) and establish genotype–phenotype correlations. (NCT06791369 chunk 1)

Visual evidence (muscle MRI and subtype comparison)

The Orphanet review provides a figure illustrating genotype-associated thigh muscle MRI patterns and a table comparing SEPN1-related vs RYR1-related MmD clinical and histopathologic features. (jungbluth2007multiminicoredisease media eac91681, jungbluth2007multiminicoredisease media f3b69ea4)

Summary tables

Table: This table summarizes the main Multiminicore disease subtypes, identifiers, causal genes, hallmark clinical and pathologic features, and notable 2023–2024 therapeutic advances. It is designed as a compact reference for knowledge-base population and downstream annotation.

Key limitations of this tool-based report

• ICD-10/ICD-11, MeSH, ORPHA, and MONDO identifiers were not present in the retrieved full-text excerpts and therefore cannot be cited here. (lillis2012clinicalutilitygene pages 1-2, jungbluth2007multiminicoredisease pages 1-2)
• Phenotype and management statistics are best-supported for SELENON/SEPN1-related myopathy (large cohort and recent trial-readiness work); equivalent large, genotype-stratified cohorts specifically labeled “RYR1-related multiminicore disease” were not retrieved in accessible form within this run. (villarquiles2020theclinicalhistologic pages 1-2, bouman2023selenonrelatedmyopathyacross pages 1-3)

References

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2. (jungbluth2007multiminicoredisease pages 1-2): Heinz Jungbluth. Multi-minicore disease. Orphanet Journal of Rare Diseases, Jul 2007. URL: https://doi.org/10.1186/1750-1172-2-31, doi:10.1186/1750-1172-2-31. This article has 165 citations and is from a peer-reviewed journal.

3. (jungbluth2007multiminicoredisease pages 5-7): Heinz Jungbluth. Multi-minicore disease. Orphanet Journal of Rare Diseases, Jul 2007. URL: https://doi.org/10.1186/1750-1172-2-31, doi:10.1186/1750-1172-2-31. This article has 165 citations and is from a peer-reviewed journal.

4. (jungbluth2007multiminicoredisease pages 2-3): Heinz Jungbluth. Multi-minicore disease. Orphanet Journal of Rare Diseases, Jul 2007. URL: https://doi.org/10.1186/1750-1172-2-31, doi:10.1186/1750-1172-2-31. This article has 165 citations and is from a peer-reviewed journal.

5. (zorzato2007functionaleffectsof pages 1-3): Francesco Zorzato, Heinz Jungbluth, Haiyan Zhou, Francesco Muntoni, and Susan Treves. Functional effects of mutations identified in patients with multiminicore disease. IUBMB Life, 59:14-20, Jan 2007. URL: https://doi.org/10.1080/15216540601187803, doi:10.1080/15216540601187803. This article has 43 citations and is from a peer-reviewed journal.

6. (villarquiles2020theclinicalhistologic pages 1-2): Rocio N. Villar-Quiles, Maja von der Hagen, Corinne Métay, Victoria Gonzalez, Sandra Donkervoort, Enrico Bertini, Claudia Castiglioni, Denys Chaigne, Jaume Colomer, Maria Luz Cuadrado, Marianne de Visser, Isabelle Desguerre, Bruno Eymard, Nathalie Goemans, Angela Kaindl, Emmanuelle Lagrue, Jürg Lütschg, Edoardo Malfatti, Michèle Mayer, Luciano Merlini, David Orlikowski, Ulrike Reuner, Mustafa A. Salih, Beate Schlotter-Weigel, Mechthild Stoetter, Volker Straub, Haluk Topaloglu, J. Andoni Urtizberea, Anneke van der Kooi, Ekkehard Wilichowski, Norma B. Romero, Michel Fardeau, Carsten G. Bönnemann, Brigitte Estournet, Pascale Richard, Susana Quijano-Roy, Ulrike Schara, and Ana Ferreiro. The clinical, histologic, and genotypic spectrum of sepn1 -related myopathy. Sep 2020. URL: https://doi.org/10.1212/wnl.0000000000010327, doi:10.1212/wnl.0000000000010327. This article has 74 citations and is from a highest quality peer-reviewed journal.

7. (bouman2023selenonrelatedmyopathyacross pages 1-3): Karlijn Bouman, Jan T. Groothuis, Jonne Doorduin, Nens van Alfen, Floris E.A. Udink ten Cate, Frederik M.A. van den Heuvel, Robin Nijveldt, Erik-Jan Kamsteeg, Anne T.M. Dittrich, Jos M.T. Draaisma, Mirian C.H. Janssen, Baziel G.M. van Engelen, Corrie E. Erasmus, and Nicol C. Voermans. Selenon-related myopathy across the life span, a cross-sectional study for preparing trial readiness. Journal of Neuromuscular Diseases, 10:1055-1074, Sep 2023. URL: https://doi.org/10.3233/jnd-221673, doi:10.3233/jnd-221673. This article has 10 citations and is from a peer-reviewed journal.

8. (villarquiles2020theclinicalhistologic pages 4-5): Rocio N. Villar-Quiles, Maja von der Hagen, Corinne Métay, Victoria Gonzalez, Sandra Donkervoort, Enrico Bertini, Claudia Castiglioni, Denys Chaigne, Jaume Colomer, Maria Luz Cuadrado, Marianne de Visser, Isabelle Desguerre, Bruno Eymard, Nathalie Goemans, Angela Kaindl, Emmanuelle Lagrue, Jürg Lütschg, Edoardo Malfatti, Michèle Mayer, Luciano Merlini, David Orlikowski, Ulrike Reuner, Mustafa A. Salih, Beate Schlotter-Weigel, Mechthild Stoetter, Volker Straub, Haluk Topaloglu, J. Andoni Urtizberea, Anneke van der Kooi, Ekkehard Wilichowski, Norma B. Romero, Michel Fardeau, Carsten G. Bönnemann, Brigitte Estournet, Pascale Richard, Susana Quijano-Roy, Ulrike Schara, and Ana Ferreiro. The clinical, histologic, and genotypic spectrum of sepn1 -related myopathy. Sep 2020. URL: https://doi.org/10.1212/wnl.0000000000010327, doi:10.1212/wnl.0000000000010327. This article has 74 citations and is from a highest quality peer-reviewed journal.

9. (villarquiles2020theclinicalhistologic pages 3-4): Rocio N. Villar-Quiles, Maja von der Hagen, Corinne Métay, Victoria Gonzalez, Sandra Donkervoort, Enrico Bertini, Claudia Castiglioni, Denys Chaigne, Jaume Colomer, Maria Luz Cuadrado, Marianne de Visser, Isabelle Desguerre, Bruno Eymard, Nathalie Goemans, Angela Kaindl, Emmanuelle Lagrue, Jürg Lütschg, Edoardo Malfatti, Michèle Mayer, Luciano Merlini, David Orlikowski, Ulrike Reuner, Mustafa A. Salih, Beate Schlotter-Weigel, Mechthild Stoetter, Volker Straub, Haluk Topaloglu, J. Andoni Urtizberea, Anneke van der Kooi, Ekkehard Wilichowski, Norma B. Romero, Michel Fardeau, Carsten G. Bönnemann, Brigitte Estournet, Pascale Richard, Susana Quijano-Roy, Ulrike Schara, and Ana Ferreiro. The clinical, histologic, and genotypic spectrum of sepn1 -related myopathy. Sep 2020. URL: https://doi.org/10.1212/wnl.0000000000010327, doi:10.1212/wnl.0000000000010327. This article has 74 citations and is from a highest quality peer-reviewed journal.

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12. (bouman2023selenonrelatedmyopathyacross pages 14-16): Karlijn Bouman, Jan T. Groothuis, Jonne Doorduin, Nens van Alfen, Floris E.A. Udink ten Cate, Frederik M.A. van den Heuvel, Robin Nijveldt, Erik-Jan Kamsteeg, Anne T.M. Dittrich, Jos M.T. Draaisma, Mirian C.H. Janssen, Baziel G.M. van Engelen, Corrie E. Erasmus, and Nicol C. Voermans. Selenon-related myopathy across the life span, a cross-sectional study for preparing trial readiness. Journal of Neuromuscular Diseases, 10:1055-1074, Sep 2023. URL: https://doi.org/10.3233/jnd-221673, doi:10.3233/jnd-221673. This article has 10 citations and is from a peer-reviewed journal.

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14. (castets2012selenoproteinnin pages 7-8): Perrine Castets, Alain Lescure, Pascale Guicheney, and Valérie Allamand. Selenoprotein n in skeletal muscle: from diseases to function. Journal of Molecular Medicine, 90:1095-1107, Apr 2012. URL: https://doi.org/10.1007/s00109-012-0896-x, doi:10.1007/s00109-012-0896-x. This article has 109 citations.

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16. (germani2024chopero1apathwayof pages 17-21): Serena GERMANI. Chop/ero1a pathway of unfolded protein response in ryr1 and sepn1-related myopathies. May 2024. URL: https://doi.org/10.25434/germani-serena_phd2024-05-30, doi:10.25434/germani-serena_phd2024-05-30. This article has 0 citations.

17. (germani2024sepn1relatedmyopathydepends pages 1-3): Serena Germani, Andrew Tri Van Ho, Alessandro Cherubini, Ersilia Varone, Alexander Chernorudskiy, Giorgia Maria Renna, Stefano Fumagalli, Marco Gobbi, Jacopo Lucchetti, Marco Bolis, Luca Guarrera, Ilaria Craparotta, Giorgia Rastelli, Giorgia Piccoli, Cosimo de Napoli, Leonardo Nogara, Elena Poggio, Marisa Brini, Angela Cattaneo, Angela Bachi, Thomas Simmen, Tito Calì, Susana Quijano-Roy, Simona Boncompagni, Bert Blaauw, Ana Ferreiro, and Ester Zito. Sepn1-related myopathy depends on the oxidoreductase ero1a and is druggable with the chemical chaperone tudca. Cell Reports Medicine, 5:101439, Mar 2024. URL: https://doi.org/10.1016/j.xcrm.2024.101439, doi:10.1016/j.xcrm.2024.101439. This article has 30 citations and is from a peer-reviewed journal.

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27. (NCT00272883 chunk 1): Alan H. Beggs. Molecular and Genetic Studies of Congenital Myopathies. Boston Children's Hospital. 2003. ClinicalTrials.gov Identifier: NCT00272883

28. (NCT06791369 chunk 1): The Prevalence of RYR1-related Disease. King's College London. 2025. ClinicalTrials.gov Identifier: NCT06791369

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30. (germani2024chopero1apathwayof pages 72-75): Serena GERMANI. Chop/ero1a pathway of unfolded protein response in ryr1 and sepn1-related myopathies. May 2024. URL: https://doi.org/10.25434/germani-serena_phd2024-05-30, doi:10.25434/germani-serena_phd2024-05-30. This article has 0 citations.

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