Congenital myaesthenic syndrome

Gene: GMPPB

Comment on phenotypes: This phenotype includes features of congenital myasthenic syndrome (in some patients) according to OMIM:615352.

Created: 2 Sep 2021, 5:13 p.m. | Last Modified: 2 Sep 2021, 5:13 p.m.

Panel Version: 2.38

Comment on phenotypes: Previous phenotypes:
Congenital Myasthenic Syndrome;muscular dystrophy-dystroglycanopathy;congenital muscular dystrophy with mental retardation;GMPPB-CMS;Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 with features of congenital myasthenic syndrome;MDDGC14 with features of CMS

Created: 22 Mar 2021, 1:56 p.m. | Last Modified: 22 Mar 2021, 1:56 p.m.

Panel Version: 2.25

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

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital Myasthenic Syndrome; muscular dystrophy-dystroglycanopathy; congenital muscular dystrophy with mental retardation; GMPPB-CMS; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 with features of congenital myasthenic syndrome; MDDGC14 with features of CMS

Comment on list classification: Updated rating from Grey to Green: 1 Green review (from gene submitter) plus >3 unrelated cases of GMPPB mutations causing congenital myasthenic phenotypes (PMID:26133662/PMID:27147698). Note that OMIM refers to these cases as MDDGC14 (MIM:615352) with features of congenital myasthenic syndrome (CMS).

Created: 6 Feb 2017, 12:37 p.m.

Comment on phenotypes: Mutations in GMPPB cause Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (615350), Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 (615351) and Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (615352).

Created: 2 Feb 2017, 2:03 p.m.

Comment on mode of inheritance: Mode of inheritance confirmed by PMID:26133662 which reports homozygous and compound heterozygous mutations in GMPPB-CMS patients.

Created: 2 Feb 2017, 2:01 p.m.

Belaya et al., 2015 (PMID:26133662) and Rodríguez Cruz et al., 2016 (PMID:27147698) describe work with D. Beeson reporting patients with a subtype of Congenital myasthenic syndrome (CMS) due to mutations in GMPPB. Patients show a predominantly limb-girdle pattern of muscle weakness, with (unlike other forms of CMS) minimal/no facial and occular symptoms. Patients are from 6 different families (5 European and 1 consangineous Iranian family).

Created: 2 Feb 2017, 1:58 p.m.

Green List (high evidence)

Screening available through Oxford Congenital Myasthenia Service

Created: 27 Jan 2017, 4:48 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital Myasthenic Syndrome; muscular dystrophy-dystroglycanopathy; congenital muscular dystrophy with mental retardation

Publications

• PMID: 26133662
• PMID: 27147698

Variants in this GENE are reported as part of current diagnostic practice