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@ARTICLE{Schlipf:144896,
author = {Schlipf, Nina A and Schüle, Rebecca and Klimpe, Sven and
Karle, Kathrin N and Synofzik, Matthis and Wolf, Julia and
Riess, Olaf and Schöls, Ludger and Bauer, Peter},
title = {{AP}5{Z}1/{SPG}48 frequency in autosomal recessive and
sporadic spastic paraplegia.},
journal = {Molecular genetics $\&$ genomic medicine},
volume = {2},
number = {5},
issn = {2324-9269},
address = {Chichester [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2020-00305},
pages = {379-382},
year = {2014},
abstract = {Hereditary spastic paraplegias (HSP) constitute a rare and
highly heterogeneous group of neurodegenerative disorders,
defined clinically by progressive lower limb spasticity and
pyramidal weakness. Autosomal recessive HSP as well as
sporadic cases present a significant diagnostic challenge.
Mutations in AP5Z1, a gene playing a role in intracellular
membrane trafficking, have been recently reported to be
associated with spastic paraplegia type 48 (SPG48). Our
objective was to determine the relative frequency and
clinical relevance of AP5Z1 mutations in a large cohort of
127 HSP patients. We applied a targeted next-generation
sequencing approach to analyze all coding exons of the AP5Z1
gene. With the output of high-quality reads and a mean
coverage of 51-fold, we demonstrated a robust detection of
variants. One 43-year-old female with sporadic complicated
paraplegia showed two heterozygous nonsynonymous variants of
unknown significance (VUS3; p.[R292W];[(T756I)]). Thus,
AP5Z1 gene mutations are rare, at least in Europeans. Due to
its low frequency, systematic genetic testing for AP5Z1
mutations is not recommended until larger studies are
performed to add further evidence. Our findings demonstrate
that amplicon-based deep sequencing is technically feasible
and allows a compact molecular characterization of multiple
HSP patients with high accuracy.},
cin = {Ext HIH / AG Gasser / Ext UKT / AG Schöls},
ddc = {610},
cid = {I:(DE-2719)5000057 / I:(DE-2719)1210000 /
I:(DE-2719)5000058 / I:(DE-2719)5000005},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25333062},
pmc = {pmc:PMC4190872},
doi = {10.1002/mgg3.87},
url = {https://pub.dzne.de/record/144896},
}