Congenital myaesthenic syndrome

Gene: LRP4

Green List (high evidence)

LRP4 (LDL receptor related protein 4)
EnsemblGeneIds (GRCh38): ENSG00000134569
EnsemblGeneIds (GRCh37): ENSG00000134569
OMIM: 604270, Gene2Phenotype
LRP4 is in 11 panels

4 reviews

Louise Daugherty (Genomics England Curator)

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.

Michael Oldridge (NHS)

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; Myasthenic syndrome, congenital, 17, 616304

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from grey to Green based on 1 Green rating from expert reviewer and discussion with curation team. 2 unrelated cases plus mouse model.
Created: 7 Feb 2017, 4:17 p.m.
Mouse models: Shen et al. (2013, 24200689) found that mice with anti-Lrp4 antibodies showed symptoms associated with myasthenia gravis (254200), including muscle weakness. Barik et al. (2014, PMID:25319686) found that conditional knockdown of the Lrp4 gene in adult mouse skeletal muscle resulted in progressive loss of muscle mass and strength, scoliosis, and ultimately death, consistent with a myasthenic phenotype.
Created: 2 Feb 2017, 2:59 p.m.
Comment on phenotypes: Mutations in LRP4 also cause the bone diseases Cenani-Lenz syndactyly syndrome (MIM:212780) and Sclerosteosis 2 (MIM:614305).
Created: 2 Feb 2017, 2:18 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by PMID:24234652 and PMID:26052878.
Created: 2 Feb 2017, 2:17 p.m.
Selcen et al., 2015 (PMID:26052878) identified a second case of CMS due to mutations in LRP4. They investigated two adult sisters with CMS affecting the limb-girdle muscles, and identified a homozygous p.Glu1233Ala mutation in LRP4 in both patients. The unaffected brother and the mother are heterozygous for the mutation.
Created: 2 Feb 2017, 2:16 p.m.
Ohkawara et al., 2014 (PMID:24234652) propose LRP4 as a new congenital myasthenic syndromes (CMS) gene, and describe a patient harboring two heteroallelic loss-of-function mutations (c.3697G>A, p.Glu1233Lys and c.3830G>A, p.Arg1277His) in LRP4. The father was heterozygous for p.Glu1233Lys. A half-brother carried no mutaion. No DNA was available from the mother.
Created: 2 Feb 2017, 2:16 p.m.

David Beeson (Oxford University)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myasthenic syndrome; Cenani-Lenz syndrome; Congental syndactyly

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Congenital myasthenic syndrome
  • Myasthenic syndrome, congenital, 17, 616304
OMIM
604270
Clinvar variants
Variants in LRP4
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

10 May 2019, Gel status: 4

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: LRP4 were set to PMID: 24234652; PMID: 26052878

29 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to LRP4.

29 Apr 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to LRP4. Rating Changed from Green List (high evidence) to Green List (high evidence)

22 Feb 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.

7 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

7 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LRP4 were set to Congenital myasthenic syndrome; Myasthenic syndrome, congenital, 17, 616304

2 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LRP4 were set to Congenital myasthenic syndrome; ?Myasthenic syndrome, congenital, 17, 616304

2 Feb 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for LRP4 was changed to BIALLELIC, autosomal or pseudoautosomal

2 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LRP4 were set to Congenital myasthenic syndrome; Cenani-Lenz syndrome; Congental syndactyly; ?Myasthenic syndrome, congenital, 17, 616304

27 Jan 2017, Gel status: 0

Added New Source

David Beeson (Oxford University)

LRP4 was added to Congenital myaestheniapanel. Sources: Eligibility statement prior genetic testing

27 Jan 2017, Gel status: 0

Created

David Beeson (Oxford University)

LRP4 was created by [email protected]