Miyoshi myopathy

Summary

Miyoshi myopathy (MONDO:0009685) is a disease with 1 cohort gene and 5 clinical trials. Top therapeutic interventions include deflazacort.

At a glance

• Prevalence: 1-9 / 1 000 000 (United Kingdom) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 25
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.22	Japan	Validated
Point prevalence	1-9 / 1 000 000	0.26	United Kingdom	Validated
Point prevalence	1-9 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

25 HPO clinical features (Orphanet curated; top 25 by frequency):

HPO ID	Term	Frequency
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0003547	Shoulder girdle muscle weakness	Frequent (30-79%)
HP:0003551	Difficulty climbing stairs	Frequent (30-79%)
HP:0003698	Difficulty standing	Frequent (30-79%)
HP:0003731	Quadriceps muscle weakness	Frequent (30-79%)
HP:0003738	Exercise-induced myalgia	Frequent (30-79%)
HP:0003749	Pelvic girdle muscle weakness	Frequent (30-79%)
HP:0007126	Proximal amyotrophy	Frequent (30-79%)
HP:0007149	Distal upper limb amyotrophy	Frequent (30-79%)
HP:0008944	Distal lower limb amyotrophy	Frequent (30-79%)
HP:0008963	Tibialis muscle weakness	Frequent (30-79%)
HP:0008994	Proximal muscle weakness in lower limbs	Frequent (30-79%)
HP:0009053	Distal lower limb muscle weakness	Frequent (30-79%)
HP:0011399	Tibialis atrophy	Frequent (30-79%)
HP:0002505	Loss of ambulation	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0008981	Calf muscle hypertrophy	Occasional (5-29%)
HP:0009027	Foot dorsiflexor weakness	Occasional (5-29%)
HP:0030051	Tip-toe gait	Occasional (5-29%)
HP:0031108	Triceps weakness	Occasional (5-29%)
HP:0200101	Decreased/absent ankle reflexes	Occasional (5-29%)
HP:0001626	Abnormality of the cardiovascular system	Excluded (0%)
HP:0002747	Respiratory insufficiency due to muscle weakness	Excluded (0%)
HP:0003552	Muscle stiffness	Excluded (0%)
HP:0008954	Intrinsic hand muscle atrophy	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Miyoshi myopathy
Mondo ID	MONDO:0009685
MeSH	C537480
OMIM	254130
Orphanet	45448
DOID	DOID:0070198
NCIT	C118846
UMLS	C5553104
MedGen	1790866
GARD	0009676
Is cancer (heuristic)	no

Also known as: Miyoshi distal myopathy · Miyoshi muscular dystrophy · Miyoshi muscular dystrophy 1 · Miyoshi muscular dystrophy type 1 · MM · MMD1 · muscular dystrophy, distal, late onset, autosomal recessive

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record · 18 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › distal myopathy › Miyoshi myopathy

Related subtypes (10): myopathy, distal, infantile-onset, MYH7-related skeletal myopathy, distal myopathy with anterior tibial onset, myopathy, distal, 5, myopathy, distal, with rimmed vacuoles, autosomal dominant distal myopathy, nebulin-related early-onset distal myopathy, myopathy, distal, 7, adult-onset, X-linked, oculopharyngodistal myopathy, asymptomatic hyperckemia-myalgia-rhabdomyolysis syndrome

Subtypes (3): Miyoshi muscular dystrophy 2, Miyoshi muscular dystrophy 3, Miyoshi muscular dystrophy 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

1 likely benign, 1 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
500004	NM_001130987.2(DYSF):c.794C>T (p.Pro265Leu)	DYSF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288008	NM_001130987.2(DYSF):c.2402C>T (p.Ala801Val)	DYSF	Likely benign	reviewed by expert panel
94341	NM_001130987.2(DYSF):c.5743G>A (p.Asp1915Asn)	DYSF	Benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DYSF	Strong	Autosomal recessive	distal myopathy with anterior tibial onset	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DYSF	Orphanet:178400	Distal myopathy with anterior tibial onset
DYSF	Orphanet:199329	Congenital myopathy, Paradas type
DYSF	Orphanet:268	Dysferlin-related limb-girdle muscular dystrophy R2
DYSF	Orphanet:45448	Miyoshi myopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DYSF	HGNC:3097	ENSG00000135636	O75923	Dysferlin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYSF	Dysferlin	Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYSF	Other/Unknown	no		C2_dom, Peroxin/Ferlin, Ferlin_A-domain

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	1
hindlimb stylopod muscle	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYSF	257	ubiquitous	marker	blood, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DYSF	1,776

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYSF	O75923	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Smooth Muscle Contraction	1	265.6×	0.004	DYSF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
monocyte activation involved in immune response	1	16852.0×	2e-04	DYSF
macrophage activation involved in immune response	1	1123.5×	0.001	DYSF
negative regulation of phagocytosis	1	991.3×	0.001	DYSF
regulation of neurotransmitter secretion	1	766.0×	0.001	DYSF

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DYSF	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DYSF

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DYSF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00527228	PHASE2/PHASE3	COMPLETED	Deflazacort in Dysferlinopathies
NCT04824040	Not specified	ENROLLING_BY_INVITATION	Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy (LGMD R2) in the RF
NCT01459302	Not specified	WITHDRAWN	Genetic Study of Familial and Sporadic ALS/Motor Neuron Disease, Miyoshi Myopathy and Other Neuromuscular Disorders
NCT01676077	Not specified	UNKNOWN	Clinical Outcome Study for Dysferlinopathy
NCT06507215	Not specified	COMPLETED	Dysferlinopathy Protein in Peripheral Blood Monocytes.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEFLAZACORT	4	1