Hereditary spastic paraplegia - childhood onset

Gene: GJC2

Amber List (moderate evidence)

GJC2 (gap junction protein gamma 2)
EnsemblGeneIds (GRCh38): ENSG00000198835
EnsemblGeneIds (GRCh37): ENSG00000198835
OMIM: 608803, Gene2Phenotype
GJC2 is in 18 panels

3 reviews

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Red List (low evidence)

Single family with adult onset reported. Additional very late onset biallelic patient identified using Sheffield panel.
Created: 9 May 2019, 5:28 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

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

Louise Daugherty (Genomics England Curator)

I don't know

Red gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Amber rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Created: 21 May 2019, 4:50 p.m.
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:54 p.m.
Red rating on Hereditary spastic paraplegia panel 1.198

Lots of accounts linking this gene with "Pelizaeus-Merzbacher-like" disorder. Needs more expert curation in case PLP is a ddx for HSP, but given that PLP1 isnt in HSP panel this looks unlikely
Chris Buxton (North Bristol NHS Trust), 27 Nov 2018. Amber rating submitted.

This gene is on the Hereditary Spastic Paraplagia (HSP) NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual: "GJC2 encodes a gap junction protein which plays a key role in central myelination and is involved in peripheral myelination in humans. Mutations in this gene have been associated with autosomal recessive Pelizaeus-Merzbacher-like disease-1 (SPG44)." It is a confirmed DD gene for spastic paraplegia 44, with monoallelic inheritance (OMIM states recessive inheritance).
Ellen McDonagh (Genomics England Curator), 14 Jun 2016

Only a single family described with this phenotype, many more cases with the above phenotypes
emma baple (Genomics England Curator), 7 Feb 2016 Red rating submitted
Created: 2 May 2019, 4:01 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

reported in several unrealted families with LEUKODYSTROPHY, HYPOMYELINATING, 2 and clincial feature of spasticity, 3 affected members of an Italian family with spastic paraplegia-44 ,multiple affected members of a large 3-generation family with autosomal dominant hereditary lymphedema. In sheffield HSP panel
Created: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating,2, 608804, AR; Spastic paraplegia 44, autosomal recessive, 613206, AR; Lymphatic malformation 3, 613480, AD

History Filter Activity

21 May 2019, Gel status: 2

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Amber was added to GJC2. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

13 May 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: GJC2 were set to Orthmann-Murphy et al. (2009)

13 May 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to GJC2.

2 May 2019, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: gjc2 has been classified as Red List (Low Evidence).

28 Apr 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: GJC2 were changed from Spastic paraplegia 44, autosomal recessive to Spastic paraplegia 44, autosomal recessive; Leukodystrophy, hypomyelinating,2, 608804, AR; Spastic paraplegia 44, autosomal recessive, 613206, AR; Lymphatic malformation 3, 613480, AD

28 Apr 2019, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: GJC2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

28 Apr 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: gjc2 has been classified as Green List (High Evidence).

28 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to GJC2.

28 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to GJC2.

3 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes Spastic paraplegia 44, autosomal recessive for gene: GJC2

28 Jan 2019, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Rebecca Foulger: Comment on list classification

19 Dec 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Sarah Leigh (Genomics England Curator)

gene: GJC2 was added gene: GJC2 was added to Hereditary spastic paraplegia - childhood onset. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Expert list,Expert Review Red Mode of inheritance for gene: GJC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GJC2 were set to Orthmann-Murphy et al. (2009) Phenotypes for gene: GJC2 were set to Spastic paraplegia 44, autosomal recessive