Disease-Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients

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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. … celý popis

Podrobná bibliografie

Hlavní autor

Anna Uhrová Mészárosová

Další autoři

Dagmar Grečmalová, Michaela Brázdilová, Nina Dvořáčková, Zdeněk Kalina, Marie Čermáková, Dagmar Vávrová, Irena Smetanová, David Staněk, Pavel Seeman

Typ dokumentu

Články

Publikováno v

Annals of human genetics. -- ISSN 1469-1809. -- Roč. 81, č. 6 (2017), s. 249-257

Témata

mladiství

dítě

Česká republika

mutační analýza DNA

exony

ženské pohlaví

proteiny vázající GTP > genetika

lidé

kojenec

introny

mužské pohlaví

membránové proteiny > genetika

lidé středního věku

missense mutace

rodokmen

spastická paraplegie dědičná > genetika

mladý dospělý

časopisecké články

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