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RT\u2010PCR and cDNA Sanger sequencing were performed on RNA extracted from patient's fibroblasts, as well as western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel missense variant in <jats:italic>SPG7<\/jats:italic> (c.2195T&gt;\u00a0C; p.Leu732Pro) was first found by whole\u2010exome sequencing (WES), while the second, also unreported, deep intronic variant (c.286\u00a0+\u00a0853A&gt;G) was identified by whole\u2010genome sequencing (WGS). RT\u2010PCR confirmed the <jats:italic>in silico<\/jats:italic> predictions showing that this variant activated a cryptic splice site, inducing the inclusion of a pseudoexon into the mRNA sequence, which encoded a premature stop codon. Western blot showed decreased SPG7 levels in patient's fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Identification of a deep intronic variant in <jats:italic>SPG7<\/jats:italic>, which could only have been detected by performing WGS, led to a diagnosis in this HSP patient. This case challenges the notion of an autosomal dominant inheritance for <jats:italic>SPG7<\/jats:italic>, and illustrates the importance of performing WGS subsequently or alternatively to WES to find additional mutations, especially in patients carrying one variant in a gene causing a predominantly autosomal recessive disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50967","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T04:38:26Z","timestamp":1576730306000},"page":"105-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A deep intronic splice variant advises reexamination of presumably dominant <i>SPG7<\/i> Cases"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3856-2060","authenticated-orcid":false,"given":"Edgard","family":"Verdura","sequence":"first","affiliation":[{"name":"Neurometabolic Diseases Laboratory Bellvitge Biomedical 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