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Disease-Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients
AU. Mészárosová, D. Grečmalová, M. Brázdilová, N. Dvořáčková, Z. Kalina, M. Čermáková, D. Vávrová, I. Smetanová, D. Staněk, P. Seeman,
Language English Country England, Great Britain
Document type Journal Article
Grant support
NV16-31921A
MZ0
CEP Register
Digital library NLK
Full text - Article
NLK
Medline Complete (EBSCOhost)
from 2003-01-01 to 1 year ago
Wiley Free Content
from 1997 to 2 years ago
PubMed
28736820
DOI
10.1111/ahg.12206
Knihovny.cz E-resources
- MeSH
- Child MeSH
- Exons MeSH
- Introns MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Membrane Proteins genetics MeSH
- Mutation, Missense MeSH
- Adolescent MeSH
- Young Adult MeSH
- DNA Mutational Analysis MeSH
- GTP-Binding Proteins genetics MeSH
- Pedigree MeSH
- Spastic Paraplegia, Hereditary genetics MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Variants in the ATL1 gene have been repeatedly described as the second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. Variants in ATL1 have been described mainly in patients with early onset HSP. We performed Sanger sequencing of all coding exons and adjacent intron regions of the ALT1 gene in 111 Czech patients with pure form of HSP and additional Multiplex-Ligation Probe Analysis (MLPA) testing targeting the ATL1 gene in 56 of them. All patients except seven were previously tested by Sanger sequencing of the SPAST gene with negative results. ATL1 diagnostic testing revealed only five missense variants in the ATL1 gene. Four of them are novel, but we suppose only two of them to be pathogenic and causal. The remaining variants are assumed to be benign. MLPA testing in 56 of sequence variant negative patients revealed no gross deletion in the ATL1 gene. Variants in the ATL1 gene are more frequent in patients with early onset HSP, but in general the occurrence of pathogenic variants in the ATL1 gene is low in our cohort, less than 4.5% and less than 11.1% in patients with onset before the age of ten. Variants in the ATL1 gene are a less frequent cause of HSP among Czech patients than has been previously reported among other populations.
Centre for Medical Genetics and Reproductive Medicine GENNET Prague Czech Republic
Department of Medical Genetics Faculty Hospital Brno Brno Czech Republic
Department of Medical Genetics Faculty Hospital Ostrava Ostrava Czech Republic
References provided by Crossref.org
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- $a Variants in the ATL1 gene have been repeatedly described as the second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. Variants in ATL1 have been described mainly in patients with early onset HSP. We performed Sanger sequencing of all coding exons and adjacent intron regions of the ALT1 gene in 111 Czech patients with pure form of HSP and additional Multiplex-Ligation Probe Analysis (MLPA) testing targeting the ATL1 gene in 56 of them. All patients except seven were previously tested by Sanger sequencing of the SPAST gene with negative results. ATL1 diagnostic testing revealed only five missense variants in the ATL1 gene. Four of them are novel, but we suppose only two of them to be pathogenic and causal. The remaining variants are assumed to be benign. MLPA testing in 56 of sequence variant negative patients revealed no gross deletion in the ATL1 gene. Variants in the ATL1 gene are more frequent in patients with early onset HSP, but in general the occurrence of pathogenic variants in the ATL1 gene is low in our cohort, less than 4.5% and less than 11.1% in patients with onset before the age of ten. Variants in the ATL1 gene are a less frequent cause of HSP among Czech patients than has been previously reported among other populations.
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