Hereditary spastic paraplegia - childhood onset
Gene: TECPR2
SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominentCreated: 20 Sep 2020, 7:15 a.m. | Last Modified: 20 Sep 2020, 7:15 a.m.
Panel Version: 2.15
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spastic paraplegia 49, autosomal recessive, 615031; Autonomic-sensory neuropathy
Publications
Variants in this GENE are reported as part of current diagnostic practice
Childhood onset, one or two families reported. Suggested in Heimer et al 2016 PMID 26542466 not a form of HSP.Created: 10 May 2019, 10:25 a.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 and Amber 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
Oz-Levi (2012, 23176824 ), ?founder fs deletion in Jewish Bukharian families with HSP-related phenotype. Some functional studies supporting an association. Zhu (2015, 25590979), different homozygous fs deletion. Pt had overlapping manifestations with SPG49. No functional studies. Currently included in Sheffield's HSP panel
Chris Buxton (North Bristol NHS Trust), 27 Nov 2018. Submitted Amber rating.
PMID:26542466 (2016) report 3 additional patients from unrelated non-Bukharian families, harboring two novel variants (c.1319delT, c.C566T) in TECPR2, suggesting that variants are not restricted to Bukharian origin.
Rebecca Foulger (Genomics England curator), 31 Oct 2017
Comment when marking as ready: limited evidence founder Jewish mutation
emma baple (Genomics England Curator), 10 May 2016Created: 2 May 2019, 4:52 p.m.
delayed motor development, spastic paraparesis, gastroesophageal reflux, and recurrent apneic episodes. affected members of 3 Jewish Bukharian families with autosomal recessive spastic paraplegia-49. In sheffield HSP panelCreated: 28 Apr 2019, 4:16 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spastic paraplegia 49, autosomal recessive, 615031
Source Expert Review Amber was added to TECPR2. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Source Yorkshire and North East GLH was added to TECPR2.
Gene: tecpr2 has been classified as Red List (Low Evidence).
Gene: tecpr2 has been classified as Green List (High Evidence).
Source NHS GMS was added to TECPR2.
Source London North GLH was added to TECPR2.
Added phenotypes Spastic paraplegia 49, autosomal recessive, 615031 for gene: TECPR2
Rebecca Foulger: Comment on list classification
gene: TECPR2 was added gene: TECPR2 was added to Hereditary spastic paraplegia - childhood onset. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Red Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TECPR2 were set to 23176824; 26542466 Phenotypes for gene: TECPR2 were set to Spastic paraplegia 49, autosomal recessive, 615031