Congenital disorder of glycosylation type Ia in a Chinese family: Function analysis of a novel PMM2 complex heterozygosis mutation

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

doi:10.1016/j.ymgmr.2024.101067

Congenital disorder of glycosylation type Ia in a Chinese family: Function analysis of a novel PMM2 complex heterozygosis mutation

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

Authors

Dan Zhong¹, Xiujuan Huang², Taoshan Feng¹, Jieqing Zeng¹, Shanshan Gu¹, Fan Ning¹, Yue Yang², Jinyuan Zhu², Yajun Wang³, Riling Chen^{1

4}, Guoda Ma¹

Affiliations

¹ Maternal and Children's Health Research Institute, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan 528300, China.
² Department of Child Healthcare, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan 528300, China.
³ Institute of Respiratory, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan 528300, China.
⁴ Department of Pediatrics, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan 528300, China.

Abstract

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% (p < 0.05) compared to the wild-type protein.

Keywords: Cerebellar dysplasia; Congenital disorder of glycosylation type Ia; Liver injury; Phosphomannomutase 2.

Publication types

Case Reports