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Title: A deep intronic splice variant advises reexamination of presumably dominant SPG7 Cases
Author: Verdura, Edgard
Schlüter, Agatha
Fernández Eulate, Gorka
Ramos-Martín, Raquel
Zulaica, Miren
Planas Serra, Laura
Ruiz, Montserrat
Fourcade, Stéphane
Casasnovas Pons, Carlos
López de Munain, Adolfo
Pujol Onofre, Aurora
Keywords: Genètica
Mutació (Biologia)
Mutation (Biology)
Issue Date: 1-Jan-2020
Publisher: Wiley
Abstract: Objective: to identify causative mutations in a patient affected by ataxia and spastic paraplegia. Methods: whole-exome sequencing (WES) and whole-genome sequencing (WGS) were performed using patient's DNA sample. RT-PCR and cDNA Sanger sequencing were performed on RNA extracted from patient's fibroblasts, as well as western blot. Results: a novel missense variant in SPG7 (c.2195T> C; p.Leu732Pro) was first found by whole-exome sequencing (WES), while the second, also unreported, deep intronic variant (c.286 + 853A>G) was identified by whole-genome sequencing (WGS). RT-PCR confirmed the in silico 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. Interpretation: identification of a deep intronic variant in SPG7, 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 SPG7, 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.
Note: Reproducció del document publicat a:
It is part of: Annals Of Clinical And Translational Neurology, 2020-01-01, vol. 7, num 1, p. 105-111
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ISSN: 2328-9503
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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