The HAND1 frameshift A126FS mutation does not cause hypoplastic left heart syndrome in mice.

ABSTRACT:

Aims

To test if a human Hand1 frame shift mutation identified in human samples is causative of hypoplastic left heart syndrome (HLHS).

Methods and results

HLHS is a poorly understood single ventricle congenital heart defect that affects two to three infants in every 10 000 live births. The aetiologies of HLHS are largely unknown. The basic helix-loop-helix transcription factor HAND1 is required for normal heart development. Interrogation of HAND1 sequence from fixed HLHS tissues identified a somatic frame-shift mutation at Alanine 126 (NP_004812.1 p.Ala126Profs13X defined as Hand1A126fs). Hand1A126fs creates a truncated HAND1 protein that predictively functions as dominant negative. To determine if this mutation is causative of HLHS, we engineered a conditional Hand1A126fs m

SUBMITTER: Firulli BA 

PROVIDER: S-EPMC5852545 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature