IEMbase 0354: POMGNT1-related muscular dystrophy-dystroglycanopathy
Scope
| Field | Value |
|---|---|
| IEMbase ID | 354 |
| Nosology | 18.2.03.03 |
| Gene | POMGNT1 |
| External IDs | OMIM:253280; OMIM:613151; OMIM:613157; ORPHA:899 |
| Generated mapping | UNMAPPED; low candidate Dystroglycanopathy.yaml |
| Candidate DisMech targets | Dystroglycanopathy.yaml#MDDG3/POMGNT1 |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents POMGNT1-CDG/muscular dystrophy-dystroglycanopathy type A3, type B3, and type C3, an autosomal recessive O-mannosylation disorder. Characteristic rows include buphthalmos, cerebral cortical malformations, increased creatine kinase, epilepsy, exophthalmia, glaucoma, megalocornea, microphthalmia, muscle-eye-brain disease, muscular dystrophy, psychomotor delay, and normal sialotransferrins.
Additional clinical rows include corpus callosum agenesis on MRI, cataract, cerebellar abnormalities, cobblestone lissencephaly, dysmorphic features, encephalocele, hydrocephalus, myopia, and pigmentary retinopathy. Biochemical rows include creatine kinase, matriglycan-specific monoclonal antibody, and sialotransferrins. No treatment rows are present.
DisMech phenotype coverage
The generated UNMAPPED status is a false negative. DisMech has a Dystroglycanopathy file that explicitly covers muscular dystrophy-dystroglycanopathy types A/B/C and the POMGNT1/MDDG3 subtype. Local mechanism describes defective O-mannosyl glycosylation of alpha-dystroglycan; POMGNT1 catalyzes addition of GlcNAc to the O-mannose M1 branch and can produce the full type A/B/C severity spectrum.
Local coverage includes muscular dystrophy, proximal weakness, neonatal hypotonia, elevated serum CK, cobblestone lissencephaly, intellectual disability, retinal dysplasia, hydrocephalus, seizures, reduced alpha-dystroglycan glycosylation, reduced laminin binding, supportive rehabilitation, genetic counseling, and emerging ribitol/AAV therapeutic context.
Concordance and completeness
Judgement: false negative; resolve to the local dystroglycanopathy POMGNT1 subtype.
The resources agree on POMGNT1 identity, autosomal recessive inheritance, O-mannosylation/alpha-dystroglycan biology, muscle-eye-brain/type A severe spectrum, muscular dystrophy, elevated CK, cortical/cobblestone brain malformations, hydrocephalus, seizures, ocular involvement, and psychomotor delay.
Curation actions
- Map this record to
Dystroglycanopathy.yaml, specifically the POMGNT1/MDDG3 subtype context. - Consider future enrichment with buphthalmos, megalocornea, microphthalmia, cataract, glaucoma, exophthalmia, myopia, pigmentary retinopathy, corpus callosum agenesis, encephalocele, muscle-eye-brain labeling, and matriglycan antibody testing after source verification.
- Treat absent IEMbase treatment rows as incomplete IEMbase coverage rather than a contradiction of local supportive and investigational therapy context.