Congenital myaesthenic syndrome

Gene: PREPL

Red List (low evidence)

Leave as Red, awaiting more information on this gene and potential disease association.

Created: 16 Oct 2019, 11:44 a.m. | Last Modified: 16 Oct 2019, 11:44 a.m.

Panel Version: 1.56

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.

I don't know

Regal et al 2014 describe a patient with myasthenic symptoms. Silva et al (29483676) describe a 2nd patient with hom PREPL variant, however, normal EMG and nerve conduction studies unlike Regal et al case (24610330 ). Regal et al 2018 (28726805) describe 5 new patients with isolated PREPL deficiency and myasthenic features (again normal EMG/nerve conduction studies in adulthood). most seem to improve in adulthood. not fatiguable. Not sure if these are true myasthenia syndromes. NB many variants are large scale deletions.

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
myasthenic syndrome; congenital myasthenic syndrome with pre- and postsynaptic features and growth hormone deficiency; ?Myasthenic syndrome, congenital, 22, 616224

Publications

• 29483676
• 28726805

Comment on phenotypes: ?Myasthenic syndrome, congenital, 22, 616224 phenotype added to OMIM in March 2017 updates.

Created: 11 May 2017, 2:40 p.m.

Added 'polygenic' tag based on PMID:24610330 in which a patient harbors a nonsense mutation in PREPL plus a deletion covering PREPL and SLC3A1 on the other allele. Note that because the patient retains one functional SLC3A1 allele, the authors do conclude that PREPL is causing the myaesthenic phenotype.

Created: 7 Feb 2017, 4:59 p.m.

Added 'treatable' tag based on PMID:24610330 which states that the myasthenic symptoms in PREPL deficiency with or without cystinuria may respond to pyridostigmine in early life.

Created: 7 Feb 2017, 3:39 p.m.

Only 1 reported case: PMID:24610330 (Regal et al., 2014) report a proband with PREPL deficiency and myasthenic symptoms. The proband harbored a paternally-inherited nonsense mutation in PREPL (p.Met270X) and a maternally inherited deletion involving both PREPL and SLC3A1. Because this patient retains one functional SLC3A1 allele, the authors conclude that her phenotype is determined by loss of both PREPL alleles.

Created: 6 Feb 2017, 11:04 a.m.

Added 'deletions' tag based on PMID:24610330 where one copy of PREPL in the proband is deleted.

Created: 6 Feb 2017, 11:03 a.m.