2026-04-13T13:41:05Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1677062025-12-05T13:05:14Zcom_2072_1057col_2072_478798col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Verdura, Edgard author Schlüter, Agatha author Fernández Eulate, Gorka author Ramos-Martín, Raquel author Zulaica, Miren author Planas Serra, Laura author Ruiz, Montserrat author Fourcade, Stéphane author Casasnovas Pons, Carlos author López de Munain, Adolfo author Pujol Onofre, Aurora author 2020-07-06T08:23:58Z 2020-07-06T08:23:58Z 2020-01-01 2020-07-06T08:15:39Z 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. Genètica Paraplegia Mutació (Biologia) Genetics Paraplegia Mutation (Biology) A deep intronic splice variant advises reexamination of presumably dominant SPG7 Cases