SPAST mutation spectrum and familial occurrence among Czech patients with pure hereditary spastic paraplegia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10332535" target="_blank" >RIV/00064203:_____/16:10332535 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/16:10332535

Result on the web

<a href="http://dx.doi.org/10.1038/jhg.2016.73" target="_blank" >http://dx.doi.org/10.1038/jhg.2016.73</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/jhg.2016.73" target="_blank" >10.1038/jhg.2016.73</a>

Result language

angličtina

Original language name

SPAST mutation spectrum and familial occurrence among Czech patients with pure hereditary spastic paraplegia

Original language description

The SPAST gene has a major role in hereditary spastic paraplegias (HSPs). This is the first report mapping characteristics of the SPAST gene in a large cohort of Czech HSP patients. All 17 coding exons of the SPAST gene were Sanger sequenced in 327 patients from 263 independent families with suspected uncomplicated HSP. The selected 126 independent patients, without mutation in the SPAST gene after Sanger sequencing, were subsequently tested by Multiplex Ligation-dependent Probe Amplification (MLPA) assay for large deletions or copy number variations affecting the SPAST gene. Among the 263 independent patients, 35 different, small mutations in 44 patients were found. Twenty-one mutations are novel with the majority of frameshift mutations. Seven mutations were found in more than one family. The age at onset ranged between preschool childhood and the fifth decade with inter-and intra-familiar differences. SPAST small mutations were detected in 16.7% (44/263) of independent tested patients. Mutations in the SPAST gene were found more frequently in familial cases (with affected relatives). Mutation were found in 31.9% (29/91 familial tested) in the familial patient group, whereas in the sporadic patient group, mutations were found in only 4.7% of cases (5/106 sporadic cases). Among SPAST-positive patients, 65.9% (29/44) were familial but only 11.4% (5/44) were sporadic. MLPA testing revealed four large deletions in four independent patients, all in familial-positive cases. Mutations in the SPAST gene are 5.8 x more frequent in familial than in sporadic cases. Large deletions were found only in familial patients. Diagnostic testing of the SPAST gene is useful only in positive family history patients not in sporadic cases.

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FH - Neurology, neuro-surgery, nuero-sciences

OECD FORD branch

—

Project

<a href="/en/project/NV15-33041A" target="_blank" >NV15-33041A: Massive parallel sequencing of genes related to infantile epilepsies and epileptic encephalopathies for diagnostics of epilepsy in Czech patients.</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Human Genetics

ISSN

1434-5161

e-ISSN

—

Volume of the periodical

61

Issue of the periodical within the volume

10

Country of publishing house

JP - JAPAN

Number of pages

6

Pages from-to

845-850

UT code for WoS article

000386341200001

EID of the result in the Scopus database

2-s2.0-84992375334