Hereditary spastic paraplegia - childhood onsetGene: MTPAP
Amber 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.
Amber rating on Hereditary spastic paraplegia panel 1.198
2 entries on HGMD Pro Crosby (2010, 20970105); variant proposed as cause of spastic paraplegia in Amish population as founder mutation. p.N478D: Slowly progressive autosomal-recessive neurodegenerative condition, the key features of which are cerebellar ataxia, spastic paraparesis, dysarthria, optic atrophy, learning difficulties. Functional studies showed loss of polyadenylation of mitochondrial transcripts Additional functional characterisation in Wilson (2014, 25008111) Al-Shamsi (2016, 27391121) Biparental, homozygous c.1468G > T (p.V490L). 2 sibs with developmental delay and regression at 8 months of age, central hypotonia, short stature, failure to thrive, cerebellar atrophy, absence-like episodes, and hip dislocation. Parents were heterozygous. no functional studies.
Chris Buxton (North Bristol NHS Trust), 27 Nov 2018 Submitted Amber rating
Created: 2 May 2019, 4:33 p.m.
2 families reported but good funcional work, 6 affected members of a large consanguineous family of Old Order Amish-FAMILY early childhood onset of progressive cerebellar ataxia, spastic paraparesis, dysarthria, and optic atrophy. In sheffield HSP panel
Created: 28 Apr 2019, 4:16 p.m.
?Spastic ataxia 4, autosomal recessive, 613672
Publications for gene: MTPAP were set to
Source Yorkshire and North East GLH was added to MTPAP.
Gene: mtpap has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MTPAP were changed from Ataxia, spastic, 4; Spastic ataxia 4, autosomal recessive to Ataxia, spastic, 4; Spastic ataxia 4, autosomal recessive; ?Spastic ataxia 4, autosomal recessive, 613672
Gene: mtpap has been classified as Green List (High Evidence).
Source NHS GMS was added to MTPAP.
Source London North GLH was added to MTPAP.
Added phenotypes Ataxia, spastic, 4; Spastic ataxia 4, autosomal recessive for gene: MTPAP
Rebecca Foulger: Comment on list classification
gene: MTPAP was added gene: MTPAP was added to Hereditary spastic paraplegia - childhood onset. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Red Mode of inheritance for gene: MTPAP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MTPAP were set to Spastic ataxia 4, autosomal recessive; Ataxia, spastic, 4