Brugada Syndrome Caused by a Large Deletion in SCN5A Only Detected by Multiplex Ligation-Dependent Probe Amplification

Lucas Eastaugh; Paul A. James; Dean Phelan; Andrew M. Davis

doi:10.1111/j.1540-8167.2010.02003.x

February 2, 2011Journal of Cardiovascular Electrophysiology

Brugada Syndrome Caused by a Large Deletion in SCN5A Only Detected by Multiplex Ligation-Dependent Probe Amplification

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Why the study?

Does multiplex ligation-dependent probe amplification detect SCN5A deletions missed by classic sequencing in a patient with Brugada syndrome?

Key Points

Identify the underlying genetic cause of severe cardiac conduction abnormalities and Brugada syndrome in a pediatric patient who tested negative on conventional genetic sequencing.
Evaluated a 14-year-old male with atrial flutter, first-degree AV block, and sinus pauses using electrocardiography and an invasive electrophysiology study (N=1).
Performed standard Sanger sequencing of the SCN5A gene followed by multiplex ligation-dependent probe amplification (MLPA) to screen for large copy number variations.
Standard SCN5A sequencing detected no pathogenic sequence variants despite inducible polymorphic ventricular tachycardia and pronounced Brugada-pattern electrocardiogram changes.
Multiplex ligation-dependent probe amplification uncovered a major gene deletion in SCN5A predicted to cause haploinsufficiency, representing the first identified large-scale rearrangement in this gene.

Structured PICO

Does multiplex ligation-dependent probe amplification detect SCN5A deletions missed by classic sequencing in a patient with Brugada syndrome?

P

Population

A 14-year-old boy presenting with atrial flutter, Brugada ECG changes, first-degree AV block, and major sinus pauses.

I

Intervention

Multiplex ligation-dependent probe amplification (MLPA)

C

Comparator

Classic sequencing for SCN5A

O

Outcome

Detection of SCN5A gene mutation/deletion

Multiplex ligation-dependent probe amplification can detect large-scale rearrangements in the SCN5A gene causing Brugada syndrome that are missed by classic sequencing.

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Implication

MLPA may detect SCN5A deletions missed by sequencing in Brugada; hypothesis-generating and should not yet change practice.

Abstract

A 14-year-old boy presented with atrial flutter. His ECG showed Brugada changes, first-degree AV block and major sinus pauses. Polymorphic VT was inducible at electrophysiology study. A pacemaker defibrillator was placed. Classic sequencing for SCN5A was normal. Multiplex ligation-dependent probe amplification, however, detected a major deletion in SCN5A. It is predicted that this deletion would result in haploinsufficiency. The report is the first description of a large-scale rearrangement of the SCN5A gene and supports the association between the molecular pathology and the phenotypic expression.

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Cite This Study

Eastaugh et al. (2011) studied this question.

synapsesocial.com/papers/6a7212d875498292b70b5291 https://doi.org/10.1111/j.1540-8167.2010.02003.x

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Brugada Syndrome Caused by a Large Deletion in SCN5A Only Detected by Multiplex Ligation-Dependent Probe Amplification

Key Points

Structured PICO

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Implication

Abstract

Discussion

Cite This Study

Brugada Syndrome Caused by a Large Deletion in SCN5A Only Detected by Multiplex Ligation-Dependent Probe Amplification

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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