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January 28, 2019Molecular Genetics & Genomic MedicineOpen Access

Identification of a pathogenic mutation in ATP2A1 via in silico analysis of exome data for cryptic aberrant splice sites

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Key result

The PANESS bioinformatics pipeline identified a homozygous ATP2A1 variant causing aberrant splicing in a family with a myotonic disorder, expanding the phenotypic spectrum beyond Brody myopathy.

Why the study?

Pathogenic mutations causing aberrant splicing are often difficult to detect because standard NGS analysis focuses on canonical splice sites.

Population

A family with a myotonic disorder

Design

Bioinformatics pipeline development and pilot study with functional validation and Drosophila disease modeling

Authors

CBChristine C. BruelsCLChengcheng LiTMTonatiuh Mendoza

Discussion

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Member takes

Overview

May support ATP2A1 testing in atypical myotonia; leaves open pipeline generalizability beyond this family.

Structured PICO

P
Population
A family with a myotonic disorder evaluated via a novel bioinformatics pipeline for cryptic aberrant splice sites.
E
Exposure
Bioinformatics pipeline (PANESS) screening of NGS data and RNAi knockdown of SERCA in Drosophila
O
Outcome
Identification of aberrant novel essential splice sites and functional validation of ATP2A1 mutation

A novel bioinformatics pipeline successfully identified a cryptic ATP2A1 splice site mutation in a family with myotonia, expanding the phenotypic spectrum beyond classic Brody myopathy.

Cite This Study

Bruels et al. (2019) studied Myotonic disorder. PANESS bioinformatics pipeline was evaluated on Identification of pathogenic mutations causing aberrant splicing. The PANESS bioinformatics pipeline identified a homozygous ATP2A1 variant causing aberrant splicing in a family with a myotonic disorder, expanding the phenotypic spectrum beyond Brody myopathy.

synapsesocial.com/papers/6a7dbb1d61f6f9a845044c19https://doi.org/10.1002/mgg3.552
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