Khalaf-Nazzal, R;
Fasham, J;
Ubeyratna, N;
Evans, DJ;
Leslie, JS;
Warner, TT;
Al-Hijawi, F;
... Crosby, AH; + view all
(2021)
Final Exon Frameshift Biallelic PTPN23 Variants Are Associated with Microcephalic Complex Hereditary Spastic Paraplegia.
Brain Sciences
, 11
(5)
, Article 614. 10.3390/brainsci11050614.
Preview |
Text
brainsci-11-00614.pdf - Published Version Download (733kB) | Preview |
Abstract
The hereditary spastic paraplegias (HSPs) are a large clinically heterogeneous group of genetic disorders classified as ‘pure’ when the cardinal feature of progressive lower limb spasticity and weakness occurs in isolation and ‘complex’ when associated with other clinical signs. Here, we identify a homozygous frameshift alteration occurring in the last coding exon of the protein tyrosine phosphatase type 23 (PTPN23) gene in an extended Palestinian family associated with autosomal recessive complex HSP. PTPN23 encodes a catalytically inert non-receptor protein tyrosine phosphatase that has been proposed to interact with the endosomal sorting complex required for transport (ESCRT) complex, involved in the sorting of ubiquitinated cargos for fusion with lysosomes. In view of our data, we reviewed previously published candidate pathogenic PTPN23 variants to clarify clinical outcomes associated with pathogenic gene variants. This determined that a number of previously proposed candidate PTPN23 alterations are likely benign and revealed that pathogenic biallelic PTPN23 alterations cause a varied clinical spectrum comprising of complex HSP associated with microcephaly, which may occur without intellectual impairment or involve more severe neurological disease. Together, these findings highlight the importance of the inclusion of the PTPN23 gene on HSP gene testing panels globally.
| Type: | Article |
|---|---|
| Title: | Final Exon Frameshift Biallelic PTPN23 Variants Are Associated with Microcephalic Complex Hereditary Spastic Paraplegia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/brainsci11050614 |
| Publisher version: | https://doi.org/10.3390/brainsci11050614 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, HSP, hereditary spastic paraplegia, PTPN23, protein tyrosine phosphatase, ESCRT, PROTEIN-TYROSINE PHOSPHATASES, TROYER-SYNDROME, MUTATIONS, HD-PTP/PTPN23, SPARTIN, DOMAIN, SPG20 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10139089 |
Archive Staff Only
 |
View Item |
