AP5Z1/SPG48 frequency in autosomal recessive and sporadic spastic paraplegia. Issue 5 (25th May 2014)

• Record Type: Journal Article
• Authors: Schlipf, Nina A.; Schüle, Rebecca; Klimpe, Sven; Karle, Kathrin N.; Synofzik, Matthis; Wolf, Julia; Riess, Olaf; Schöls, Ludger; Bauer, Peter
• Is Part Of: Molecular genetics & genomic medicine. Volume 2:Issue 5(2014:Sep.)
• Page Start: 379
• Page End: 382
• Publication Date: 2014-05-25
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.87
• Languages: English
• ISSNs: 2324-9269

Abstract

<abstract abstract-type="main" id="mgg387-abs-0001"> <title>Abstract</title> <p>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 <italic>AP5Z1</italic>, 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 <italic>AP5Z1</italic> mutations in a large cohort of 127 HSP patients. We applied a targeted next‐generation sequencing approach to analyze all coding exons of the <italic>AP5Z1</italic> 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, <italic>AP5Z1</italic> gene mutations are rare, at least in Europeans. Due to its low frequency, systematic genetic testing for <italic>AP5Z1</italic> 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.</p> </abstract>