Congenital myaesthenic syndrome

Gene: PLEC

I don't know

Review and rating from Michael Oldridge (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust), submitted by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.

Created: 30 Apr 2019, 9:30 a.m.

Green List (high evidence)

see PanelApp - not sure if Maselli paper can be used - presence of homozygous CHRNE mutn likely to be responsible for majority of CMS phenotype. But still 3 unrelated cases described. Green.

Created: 29 Apr 2019, 4:33 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myasthenic syndrome; Plectin deficiency; myasthenic syndrome; Congenital myasthenic syndrome associatedwith epidermolysis bullosa (EBS) 226670

Comment on list classification: Updated rating from Amber to Green: 3 unrelated cases (2 African American, and 1 Iranian) plus a polygenic case (PMID:21175599).

Created: 22 Feb 2017, 12:06 p.m.

Comment on mode of inheritance: Homozygous or compound het variants reported in literature.

Created: 22 Feb 2017, 10:51 a.m.

Comment on list classification: Updated rating from Red to Amber awaiting Expert feedback: 3 monogenic cases plus 1 digenic case (with CHRNE).

Created: 20 Feb 2017, 3:09 p.m.

PMID:25683118 (Fattahi et al., 2015) report an Iranian family with 2 affected sisters showing progressive limb and ocular muscle weakness (myasthenic symptoms). Compound het mutations (p.Gln1022Ter (c.3064C>T) and p.Gly3835Ser (c.11503G>A), were found in the PLEC gene.

Created: 20 Feb 2017, 3:07 p.m.

Maselli et al., 2011 (PMID:21175599) report a consanguineous Russian woman with EBS and CMS with a homozygous 36 nucleotide insertion (1506_1507ins36) in PLEC that results in a reduced expression of PLEC mRNA and plectin in the patient muscle. The patient also harboured a homozygous 1293insG mutation in CHRNE, indicating that abnormalities in both genes contribute to the CMS phenotype

Created: 20 Feb 2017, 3:04 p.m.

Added 'monogenic-polygenic' tag based on PMID:21175599 which reports on a patient with homozygous mutations in both PLEC and CHRNE.

Created: 6 Feb 2017, 12:21 p.m.

Selcen et al., 2011 (PMID:21263134) report on an African American man with epidermolysis bullosa simplex (EBS) since early infancy, and progressive muscle weakness, hyperCKemia, and myasthenic symptoms. Mutation analysis demonstrated two truncating mutations in PLEC: c.6955C>T/p.Arg2319X and c.12043dupG.

Created: 6 Feb 2017, 11:32 a.m.

Banwell et al., 1999 (PMID:10446808) report a 20-year-old African American female who with was diagnosed with epidermolysis bullosa simplex (EBS) as an infant and her myasthenic symptoms began around the age of 9 years. This is the first reporting of EBS with a myasthenic syndrome. PMID:21263134 (Selcen et al., 2011) reported that this patient carried 2 truncating mutations: c.12043dupG and a novel c.6169C>T/p.Gln2057X mutation.

Created: 6 Feb 2017, 11:31 a.m.