A deep intronic splice variant advises reexamination of presumably dominant SPG7 Cases.

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. Weste

SUBMITTER: Verdura E 

PROVIDER: S-EPMC6952318 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature