Hereditary spastic paraplegia - childhood onset

Gene: MTPAP

Amber List (moderate evidence)

MTPAP (mitochondrial poly(A) polymerase)
EnsemblGeneIds (GRCh38): ENSG00000107951
EnsemblGeneIds (GRCh37): ENSG00000107951
OMIM: 613669, Gene2Phenotype
MTPAP is in 14 panels

3 reviews

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

I don't know

Two families, childhood onset. No additional patients identified using Sheffield panel.
Created: 10 May 2019, 7:39 a.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

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.

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

Green List (high evidence)

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.

Phenotypes
?Spastic ataxia 4, autosomal recessive, 613672

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Yorkshire and North East GLH
  • Expert Review Amber
  • NHS GMS
  • London North GLH
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Ataxia, spastic, 4
  • Spastic ataxia 4, autosomal recessive
  • ?Spastic ataxia 4, autosomal recessive, 613672
OMIM
613669
Clinvar variants
Variants in MTPAP
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 May 2019, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: MTPAP were set to

13 May 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to MTPAP.

2 May 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: mtpap has been classified as Amber List (Moderate Evidence).

28 Apr 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

28 Apr 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: mtpap 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 MTPAP.

28 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to MTPAP.

3 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes Ataxia, spastic, 4; Spastic ataxia 4, autosomal recessive for gene: MTPAP

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 Phenotypes

Sarah Leigh (Genomics England Curator)

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