A novel de novo splicing mutation c.1444-2A>T in the TSC2 gene causes exon skipping and premature termination in a patient with tuberous sclerosis syndrome.
TSC2 gene
in silico prediction
mRNA analysis
novel splice site mutation
tuberous sclerosis complex (TSC) syndrome
Journal
IUBMB life
ISSN: 1521-6551
Titre abrégé: IUBMB Life
Pays: England
ID NLM: 100888706
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
08
06
2019
accepted:
04
07
2019
pubmed:
19
7
2019
medline:
8
7
2020
entrez:
19
7
2019
Statut:
ppublish
Résumé
Tuberous sclerosis complex (TSC) syndrome is a neurocutaneous syndrome that affects the brain, skin, and kidneys that has an adverse impact on the patient's health and quality of life. There have been several recent advances that elucidate the genetic complex of this disorder that will help understand the basic neurobiology of this disorder. We report a Tunisian patient with clinical manifestations of TSC syndrome. We investigated the causative molecular defect in this patient using PCR followed by direct sequencing. Subsequently, in silico studies and mRNA analysis were performed to study the pathogenicity of the new variation found in the TSC2. Bioinformatics tools predicted that the novel mutation c.1444-2A>T have pathogenic effects on splicing machinery. RT-PCR followed by sequencing revealed that the mutation c.1444-2A>T generates two aberrant transcripts. The first, with exon 15 skipping, is responsible for the loss of 52 amino acids, which causes the production of an aberrant protein isoform. The second, with the inclusion of 122 nucleotides of intron 14, is responsible for the creation of new premature termination codons (TGA), which causes the production of a truncated TSC2 protein. This study highlighted the clinical features of a Tunisian patient with TSC syndrome and revealed a splicing mutation c.1444-2A>T within intron 14 of TSC2 gene, which is present for the first time using Sanger sequencing approach, as a disease-causing mutation in a Tunisian patient with TSC syndrome.
Substances chimiques
Protein Isoforms
0
TSC2 protein, human
0
Tuberous Sclerosis Complex 2 Protein
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1937-1945Informations de copyright
© 2019 International Union of Biochemistry and Molecular Biology.
Références
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