Childhood onset hereditary spastic paraplegia
Gene: GJC2
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
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 submittedCreated: 2 May 2019, 4:01 p.m.
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 panelCreated: 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
Mode of inheritance for gene: GJC2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Source Expert Review Amber was added to GJC2. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Publications for gene: GJC2 were set to Orthmann-Murphy et al. (2009)
Source Yorkshire and North East GLH was added to GJC2.
Gene: gjc2 has been classified as Red List (Low Evidence).
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
Mode of inheritance for gene: GJC2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: gjc2 has been classified as Green List (High Evidence).
Source NHS GMS was added to GJC2.
Source London North GLH was added to GJC2.
Added phenotypes Spastic paraplegia 44, autosomal recessive for gene: GJC2
Rebecca Foulger: Comment on list classification
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