Myasthenic syndrome, congenital, 4a, slow-channel

Preferred Label : Myasthenic syndrome, congenital, 4a, slow-channel;

Symbol : CMS4A;

CISMeF acronym : CMS1A1; CMS4A;

Type : Phenotype, molecular basis known;

Alternative titles and symbols : Congenital myasthenic syndrome type ia1; Cms ia1; CMS1A1;

Description : For a discussion of genetic heterogeneity of congenital myasthenic syndrome (CMS), see 608931. See also CMS with episodic apnea (254210), which is also designated CMS Ia. Christodoulou et al. (1997) performed linkage studies in 12 families, 7 of them consanguineous, containing 36 patients with FIMG. A combination of linkage search through the genome, DNA pooling, and homozygosity mapping were employed to localize the disorder to the telomeric region of chromosome 17p. A maximum lod score of 9.28 at theta 0.034 was obtained between the disease locus and marker locus D17S1537. Haplotype analysis showed all families to be consistent with linkage to this region, thus providing evidence for genetic homogeneity of familial infantile myasthenia. Multipoint linkage analysis mapped the disease gene in the interval of approximately 4 cM between marker loci D17S1537 and D17S1298 with a maximum multipoint lod score of 12.07. Haplotype analysis and homozygosity by descent in affected individuals of the consanguineous families revealed results in agreement with the confinement of the FIM1 region within the interval between marker loci D17S1537 and D17S1298 on 17p13. Synaptobrevin-2 (185881), a synaptic vesicle protein, is encoded by a gene that has been mapped to the telomeric region of 17p, suggesting to Christodoulou et al. (1997) that the mutation responsible for FIM1 is located in that gene. Synaptobrevin probably participates in neurotransmitter release at a step between docking and fusion (Hunt et al., 1994). *FIELD* RF 1. Christodoulou, K.; Tsingis, M.; Deymeer, F.; Serdaroglu, P.; Ozdemir, C.; Al-Shehab, A.; Bairactaris, C.; Mavromatis, I.; Mylonas, I.; Evoli, A.; Kyriallis, K.; Middleton, L. T.: Mapping of the familial infantile myasthenia (congenital myasthenic syndrome type Ia) gene to chromosome 17p with evidence of genetic homogeneity. Hum. Molec. Genet. 6: 635-640, 1997. 2. Hunt, J. M.; Bommert, K.; Charlton, M. P.; Kistner, A.; Habermann, E.; Augustine, G. J.; Betz, H.: A post-docking role for synaptobrevin in synaptic vesicle fusion. Neuron 12: 1269-1279, 1994. *FIELD* CS Autosomal recessive;

Inheritance : Autosomal recessive (rare); Autosomal dominant;

Molecular basis : Caused by mutation in the cholinergic receptor, nicotinic, epsilon polypeptide gene (CHRNE, 100725.0001);

Prefixed ID : #605809;

Details

Origin ID

605809;

UMLS CUI

C4225413;

Automatic exact mappings (from CISMeF team)
- fim 1 [MeSH Supplementary Concept]
Currated CISMeF NLP mapping
- congenital myasthenic syndrome 4A [DO Concept]
- myasthenia, familial infantile, 1 [MeSH concept]
- myasthenia, familial infantile, 1 [MeSH Supplementary Concept]
DO Cross reference
- congenital myasthenic syndrome 4A [DO Concept]
Genes related to phenotype
- Cholinergic receptor, nicotinic, epsilon polypeptide [OMIM gene]
HPO term(s)
- Apneic episodes precipitated by illness, fatigue, stress [HPO term]
- Arthrogryposis multiplex in severe cases [HPO term]
- Autosomal dominant inheritance [HPO term]
- Autosomal recessive inheritance [HPO term]
- Bulbar palsy [HPO term]
- Congenital onset [HPO term]
- Decreased miniature endplate potentials [HPO term]
- Dysphagia [HPO term]
- EMG: decremental response of compound muscle action potential to repetitive nerve stimulation [HPO term]
- Easy fatigability [HPO term]
- Fatigable weakness [HPO term]
- Feeding difficulties in infancy [HPO term]
- Generalized hypotonia [HPO term]
- Generalized hypotonia due to defect at the neuromuscular junction [HPO term]
- Limb muscle weakness [HPO term]
- Myopathy [HPO term]
- Ophthalmoparesis [HPO term]
- Poor feeding due to muscle weakness [HPO term]
- Poor suck [HPO term]
- Ptosis [HPO term]
- Respiratory distress [HPO term]
- Respiratory insufficiency due to muscle weakness [HPO term]
- Strabismus [HPO term]
- Sudden episodic apnea [HPO term]
- Type 2 muscle fiber atrophy [HPO term]
- Weak cry [HPO term]
- Weakness [HPO term]
ORDO concept(s)
- Congenital myasthenic syndrome [ORDO Disease]
- Postsynaptic congenital myasthenic syndromes [ORDO Disease]
Semantic type(s)
- Disease or Syndrome [UMLS semantic type]
Validated automatic mappings to NTBT
- Congenital myasthenic syndrome [ORDO Disease]

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