UNASSIGNED: @entity299 ( @entity299 ) is the most prevalent @entity851 in @entity1 and is the most common non-infectious cause of @entity1 morbidity and mortality. Increasing evidence demonstrates that genetic defects are involved in the pathogenesis of @entity299 . However, @entity299 is genetically heterogeneous, and the genetic determinants underpinning @entity299 in most @entity1 remain unknown. In this study, the whole coding region of the @entity20195 gene (isoform c) was sequenced in 185 unrelated @entity1 with @entity299 . The available relatives of a mutation carrier and 300 unrelated healthy individuals used as controls were also genotyped for @entity20195 . The functional characteristics of the mutation were delineated by using a dual-luciferase reporter assay system. As a result, a novel heterozygous @entity20195 mutation, @entity69079 , was identified in a @entity1 with @entity215 ( @entity215 ). Genetic analysis of the index @entity1 's pedigree showed that the mutation co-segregated with @entity215 . The mutation was absent in 600 reference chromosomes. Biochemical analysis revealed that the @entity69079 -mutant @entity20195 is associated with significantly reduced transcriptional activity compared with its wild-type counterpart. Furthermore, the mutation markedly decreased the synergistic activation between @entity20195 and @entity21505 . This study firstly associates @entity20195 loss-of-function mutation with increased susceptibility to @entity215 , providing novel insight into the molecular mechanism of @entity299 .

XXXX loss-of-function mutation contributes to @entity215 .

@entity1 :: ('9606', 'Species') :: ['humans', 'patients', 'patient', 'infant'] @entity851 :: ('MESH:D006130', 'Disease') :: ['developmental abnormality'] @entity20195 :: ('5308', 'Gene') :: ['PITX2'] @entity215 :: ('MESH:D013771', 'Disease') :: ['TOF', 'tetralogy of Fallot'] @entity21505 :: ('1482', 'Gene') :: ['NKX2-5'] @entity69079 :: ('p|SUB|Q|102|L', 'ProteinMutation') :: ['p.Q102L', 'Q102L'] @entity299 :: ('MESH:D006331', 'Disease') :: ['Congenital heart disease', 'CHD']
@entity20195 :: (5308,Gene) :: ['PITX2']
