Chelban, V;
Alsagob, M;
Kloth, K;
Chirita-Emandi, A;
Vandrovcova, J;
Maroofian, R;
Davagnanam, I;
Bakhtiari, S;
AlSayed, MD;
Rahbeeni, Z;
et al.
Chelban, V; Alsagob, M; Kloth, K; Chirita-Emandi, A; Vandrovcova, J; Maroofian, R; Davagnanam, I; Bakhtiari, S; AlSayed, MD; Rahbeeni, Z; AlZaidan, H; Malintan, NT; Johannsen, J; Efthymiou, S; Ghayoor Karimiani, E; Mankad, K; Al-Shahrani, SA; Beiraghi Toosi, M; AlShammari, M; Groppa, S; Haridy, NA; AlQuait, L; Qari, A; Huma, R; Salih, MA; Almass, R; Almutairi, FB; Hamad, MH; Alorainy, IA; Ramzan, K; Imtiaz, F; Puiu, M; Kruer, MC; Bierhals, T; Wood, NW; Colak, D; Houlden, H; Kaya, N
(2020)
Genetic and phenotypic characterization of NKX6‐2‐related spastic ataxia and hypomyelination.
Eur J Neurol, 27 (2).
pp. 334-342.
ISSN 1468-1331
https://doi.org/10.1111/ene.14082
SGUL Authors: Maroofian, Reza
Abstract
Background and purpose
Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi‐allelic mutations in NKX6‐2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy.
Methods
Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6‐2 mutations in a multicentre setting is described. Then, all reported NKX6‐2 mutations and those identified in this study were combined and an in‐depth analysis of NKX6‐2‐related disease spectrum was provided.
Results
Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6‐2 were identified, evidencing a high NKX6‐2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6‐2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur.
Conclusions
NKX6‐2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6‐2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels.
Item Type: |
Article
|
Additional Information: |
© 2019 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: |
NKX6-2, SPAX8, hypomyelination, leukodystrophy, spastic ataxia 8, hypomyelination, leukodystrophy, NKX6-2, spastic ataxia 8, SPAX8, 1103 Clinical Sciences, 1109 Neurosciences, Neurology & Neurosurgery |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Eur J Neurol |
ISSN: |
1468-1331 |
Language: |
eng |
Dates: |
Date | Event |
---|
7 January 2020 | Published | 17 October 2019 | Published Online | 21 August 2019 | Accepted |
|
Publisher License: |
Publisher's own licence |
Projects: |
|
PubMed ID: |
31509304 |
Web of Science ID: |
WOS:000490756800001 |
|
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/111215 |
Publisher's version: |
https://doi.org/10.1111/ene.14082 |
Statistics
Item downloaded times since 15 Nov 2019.
Actions (login required)
|
Edit Item |