Wang Ruixue, Wang Yizhong, Yu Ronghua, Xu Wuhen, Zhang Ting, Xiao Yongmei
Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Gut Microbiota and Metabolic Research Center, Immunity and Critical Care Medicine, School of Medicine, Institute of Pediatric Infection, Shanghai Jiao Tong University, Shanghai, China.
Front Genet. 2023 Jan 9;13:1079481. doi: 10.3389/fgene.2022.1079481. eCollection 2022.
Recently, UNC45 myosin chaperone A (UNC45A) deficiency was identified as a cause of osteo-oto-hepato-enteric syndrome (O2HE) characterized by congenital diarrhea, neonatal cholestasis, deafness, and bone fragility. To date, only a few O2HE cases have been reported in the literature. Here, we present a child from China diagnosed with O2HE with novel compound heterozygous variants in . The patient suffered with neonatal jaundice, cholestasis, and intractable diarrhea after birth. Laboratory tests revealed highly elevated levels of total serum bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA). The patient was managed with ursodeoxycholic acid (UDCA)-based treatments, and the clinical symptoms and abnormal liver functions were significantly relieved. The patient's hearing was normal, and no sign of bone fragility was observed. Exome sequencing (ES) identified novel compound heterozygote variants c.292C>T (p.Arg98Trp)/c.2534-2545del (p.Leu845-Met848del) in , which were inherited from her mother and father, respectively. Both variants are predicted to be deleterious by predictors. We present an O2HE child from China with novel compound heterozygous variants in . Our patient's clinical manifestations were less severe than those of the previous reported cases, which expands the clinical spectrum of O2HE.
最近，UNC45肌球蛋白伴侣A（UNC45A）缺陷被确定为骨-耳-肝-肠综合征（O2HE）的病因，该综合征的特征为先天性腹泻、新生儿胆汁淤积、耳聋和骨质脆弱。迄今为止，文献中仅报道了少数几例O2HE病例。在此，我们报告一名来自中国的儿童，被诊断为O2HE，其存在新的复合杂合变异。该患者出生后患有新生儿黄疸、胆汁淤积和顽固性腹泻。实验室检查显示血清总胆红素（TB）、直接胆红素（DB）和总胆汁酸（TBA）水平大幅升高。该患者接受了基于熊去氧胆酸（UDCA）的治疗，临床症状和肝功能异常得到显著缓解。患者听力正常，未观察到骨质脆弱迹象。外显子组测序（ES）在[具体基因名称未给出]中鉴定出新的复合杂合变异c.292C>T（p.Arg98Trp）/c.2534-2545del（p.Leu845-Met848del），分别遗传自其母亲和父亲。两种变异经预测工具预测均为有害变异。我们报告了一名来自中国的O2HE儿童，其在[具体基因名称未给出]中存在新的复合杂合变异。我们患者的临床表现比先前报道的病例轻，这扩展了O2HE的临床谱。
