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Further evidence for POMK as candidate gene for WWS with meningoencephalocele
- Source :
- Orphanet Journal of Rare Diseases, Vol 15, Iss 1, Pp 1-10 (2020), Orphanet Journal of Rare Diseases
- Publication Year :
- 2020
-
Abstract
- Background Walker-Warburg syndrome (WWS) is a rare form of alpha-dystroglycanopathy characterized by muscular dystrophy and severe malformations of the CNS and eyes. Bi-allelic pathogenic variants in POMK are the cause of a broad spectrum of alpha-dystroglycanopathies. POMK encodes protein-O-mannose kinase, which is required for proper glycosylation and function of the dystroglycan complex and is crucial for extracellular matrix composition. Results Here, we report on male monozygotic twins with severe CNS malformations (hydrocephalus, cortical malformation, hypoplastic cerebellum, and most prominently occipital meningocele), eye malformations and highly elevated creatine kinase, indicating the clinical diagnosis of a congenital muscular dystrophy (alpha-dystroglycanopathy). Both twins were found to harbor a homozygous nonsense mutation c.640C>T, p.214* in POMK, confirming the clinical diagnosis and supporting the concept that POMK mutations can be causative of WWS. Conclusion Our combined data suggest a more important role for POMK in the pathogenesis of meningoencephalocele. Only eight different pathogenic POMK variants have been published so far, detected in eight families; only five showed the severe WWS phenotype, suggesting that POMK-associated WWS is an extremely rare disease. We expand the phenotypic and mutational spectrum of POMK-associated WWS and provide evidence of the broad phenotypic variability of POMK-associated disease.
- Subjects :
- Male
2716 Genetics (clinical)
Candidate gene
Congenital muscular dystrophy
10039 Institute of Medical Genetics
Nonsense mutation
Medizin
lcsh:Medicine
610 Medicine & health
Protein O-mannose kinase
Biology
Nervous System Malformations
Meningocele
Muscular Dystrophies
POMK
medicine
Humans
2736 Pharmacology (medical)
Pharmacology (medical)
Muscular dystrophy
Walker–Warburg syndrome
Alpha-dystroglycanopathy
Genetics (clinical)
Genetics
Walker-Warburg syndrome
Research
Homozygote
lcsh:R
Meningoencephalocele
Twins, Monozygotic
General Medicine
medicine.disease
Phenotype
Dystroglycan complex
Mutation
570 Life sciences
biology
Protein Kinases
Rare disease
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Orphanet Journal of Rare Diseases, Vol 15, Iss 1, Pp 1-10 (2020), Orphanet Journal of Rare Diseases
- Accession number :
- edsair.doi.dedup.....fd758ce1f2552820c470a9486699a21d