AUTHOR=Gao Shan-Yu , Liu Yu-Xing , Dong Yi , Fan Liang-Liang , Ding Qi , Liu Lv 

TITLE=Case report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1205052

DOI=10.3389/fgene.2023.1205052

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the <italic>WASHC5</italic> gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear.</p><p><bold>Method:</bold> We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family.</p><p><bold>Results:</bold> A novel splice-altering variant (c.712–2A&gt;G) in the <italic>WASHC5</italic> gene was detected and further verified by RNA splicing analysis and Sanger sequencing. Real-time qPCR analysis showed that the expression of genes involved in the Wiskott–Aldrich syndrome protein and SCAR homolog (WASH) complex and endosomal and lysosomal systems was altered due to this variant.</p><p><bold>Conclusion:</bold> A novel heterozygous splice-altering variant (c.712–2A&gt;G) in the <italic>WASHC5</italic> gene was detected in a Chinese family with HSP. Our study provided data for genetic counseling to this family and offered evidence that this splicing variant in the <italic>WASHC5</italic> gene is significant in causing HSP.</p>