一个中国家庭中的Ia型先天性糖基化障碍：一种新型复合杂合突变的功能分析

Zhong Dan, Huang Xiujuan, Feng Taoshan, Zeng Jieqing, Gu Shanshan, Ning Fan, Yang Yue, Zhu Jinyuan, Wang Yajun, Chen Riling, Ma Guoda

Maternal and Children's Health Research Institute, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan 528300, China.

Department of Child Healthcare, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan 528300, China.

Mol Genet Metab Rep. 2024 Feb 24;39:101067. doi: 10.1016/j.ymgmr.2024.101067. eCollection 2024 Jun.

Congenital disorder of glycosylation type Ia (CDG-Ia) is an autosomal recessive genetic disease caused by a mutation in the phosphomannomutase 2 (PMM2) gene. We have identified a 13-month-old boy who has been diagnosed with CDG-Ia. He displays several characteristic symptoms, including cerebellar hypoplasia, severe developmental retardation, hypothyroidism, impaired liver function, and abnormal serum ferritin levels. Through whole-exome sequencing, we discovered novel complex heterozygous mutations in the PMM2 gene, specifically the c.663C > G (p.F221L) mutation and loss of exon 2. Further analysis revealed that the enzymatic activity of the mutant PMM2 protein was significantly reduced by 44.97% ( < 0.05) compared to the wild-type protein.

先天性糖基化障碍Ia型（CDG-Ia）是一种常染色体隐性遗传病，由磷酸甘露糖变位酶2（PMM2）基因突变引起。我们鉴定出一名13个月大已被诊断为CDG-Ia的男孩。他表现出多种特征性症状，包括小脑发育不全、严重发育迟缓、甲状腺功能减退、肝功能受损以及血清铁蛋白水平异常。通过全外显子组测序，我们在PMM2基因中发现了新的复合杂合突变，具体为c.663C＞G（p.F221L）突变和外显子2缺失。进一步分析显示，与野生型蛋白相比，突变型PMM2蛋白的酶活性显著降低了44.97%（P＜0.05）。