Childhood onset hereditary spastic paraplegia

Gene: MTPAP

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

• 20970105
• 27391121

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

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.

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