Yagi Hisato, Lo Cecilia W
Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15201, USA.
J Cardiovasc Dev Dis. 2023 Feb 24;10(3):99. doi: 10.3390/jcdd10030099.
Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease characterized by hypoplasia of left-sided heart structures. The developmental basis for restriction of defects to the left side of the heart in HLHS remains unexplained. The observed clinical co-occurrence of rare organ situs defects such as biliary atresia, gut malrotation, or heterotaxy with HLHS would suggest possible laterality disturbance. Consistent with this, pathogenic variants in genes regulating left-right patterning have been observed in HLHS patients. Additionally, HLHS mutant mice show splenic defects, a phenotype associated with heterotaxy, and HLHS in mice arises in part from mutation in , a component of the Sin3A chromatin complex known to regulate and , genes essential for left-right patterning. Together, these findings point to laterality disturbance mediating the left-sided heart defects associated with HLHS. As laterality disturbance is also observed for other CHD, this suggests that heart development integration with left-right patterning may help to establish the left-right asymmetry of the cardiovascular system essential for efficient blood oxygenation.
左心发育不全综合征（HLHS）是一种复杂的先天性心脏病，其特征是左侧心脏结构发育不全。HLHS中缺陷仅限于心脏左侧的发育基础仍未得到解释。观察到的HLHS与罕见器官位置缺陷（如胆道闭锁、肠道旋转不良或内脏反位）的临床共现提示可能存在左右侧性紊乱。与此一致的是，在HLHS患者中观察到了调节左右模式的基因的致病变异。此外，HLHS突变小鼠表现出脾脏缺陷，这是一种与内脏反位相关的表型，小鼠中的HLHS部分源于Sin3A染色质复合物成分的突变，该复合物已知可调节左右模式的关键基因和。总之，这些发现表明左右侧性紊乱介导了与HLHS相关的左侧心脏缺陷。由于在其他先天性心脏病中也观察到了左右侧性紊乱，这表明心脏发育与左右模式的整合可能有助于建立对有效血液氧合至关重要的心血管系统的左右不对称性。
