Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
June 18, 2026GenesOpen Access

Two novel truncating HAND2 variants co-segregate with familial and idiopathic AF.

View Full Paper
Ask AI
Bookmark
Share

Why the study?

Do truncating HAND2 variants predispose individuals to atrial fibrillation?

Population

A four-generation pedigree with familial atrial fibrillation, a cohort of 238 subjects with idiopathic AF…

Comparison

Pan-exome sequencing, Sanger sequencing, and in… vs 266 healthy individuals (control group).

Design

Case-control

Key result

Two novel heterozygous truncating HAND2 variants (p.Trp46* and p.Gln113*) were discovered in an AF pedigree and one idiopathic AF case, co-segregating with the AF phenotype and absent in 266 controls.

Authors

HZHong ZhangXHXiao-Qing HuNLNing Li

Discussion

Loading...

Member takes

Overview

Truncating HAND2 variants may predispose to AF; hypothesis-generating and requires replication before clinical adoption.

Key Points

  • Investigate the role of HAND2 genetic variants in familial and idiopathic atrial fibrillation.
  • Four-generation pedigree with familial atrial fibrillation and 238 idiopathic AF patients; 266 healthy controls enrolled.
  • Pan-exome sequencing performed on AF pedigree members; Sanger sequencing for all subjects.
  • Functional effects assessed using in vitro dual-reporter gene assays.
  • Two novel heterozygous truncating HAND2 variants identified: c.138G>A (Trp46*) and c.337C>T (Gln113*).
  • Both variants co-segregated with atrial fibrillation phenotype; absent in control chromosomes.
  • Trp46* and Gln113* mutants failed to activate HCN4 and NPPA, critical genes linked to AF.

Study Design

Type

Case-Control (n=504)

Structured PICO

Do truncating HAND2 variants predispose individuals to atrial fibrillation?

P
Population
A four-generation pedigree with familial AF, 238 subjects with idiopathic AF, and 266 healthy controls.
E
Exposure
Pan-exome sequencing, Sanger sequencing, and in vitro dual-reporter gene measurement to detect and functionally assess HAND2 variations.
C
Comparator
266 healthy individuals (control group).
O
Outcome
Identification of HAND2 variations and their functional effects on the transcriptional activation of HCN4 and NPPA.surrogate

Novel truncating variants in the HAND2 gene predispose individuals to atrial fibrillation by impairing the transcriptional activation of AF-causative genes HCN4 and NPPA.

Cite This Study

Zhang et al. (2026) conducted a case-control in Atrial fibrillation (n=504). Truncating HAND2 variants (p.Trp46* and p.Gln113*) vs. Absence of variants (healthy controls) was evaluated on Presence of HAND2 variations and their functional effects. Two novel heterozygous truncating HAND2 variants (p.Trp46* and p.Gln113*) were discovered in an AF pedigree and one idiopathic AF case, co-segregating with the AF phenotype and absent in 266 controls.

synapsesocial.com/papers/6a33cfcf14a9c556e66778c0https://doi.org/10.3390/genes17060701
View Full Paper
Ask AI
Bookmark
Share