Identification of Two Novel Mutations in COG5 Causing Congenital Disorder of Glycosylation

Frontiers in Genetics

Chun-Hua Jin¹  Jian-Hong Wang¹  Xiao-Meng Li¹  Lin Wang¹  Xi Wang¹  Xiao-Yan Wang¹  Lin Han² 

[1] Department of Preventive Health Care, Children’s Hospital, Capital Institute of Pediatrics, Beijing, China;Running Gene Inc., Beijing, China.;

关键词: COG5 gene;    congenital disorder of glycosylation;    psychomotor delay;    ataxia;    visual abnormalities;    genetic sequencing;   

DOI  :  10.3389/fgene.2020.00168

来源: DOAJ

【 摘 要 】

ObjectiveThis study reports a Chinese patient with a Congenital Disorder of Glycosylation (CDG) caused by compound-heterozygous mutations in the Conserved Oligomeric Golgi 5 (COG5) gene and thereby offers concrete evidence for early diagnosis.MethodsThe clinical manifestations, the results of laboratory examinations and genetic analysis of a 4-year-old Chinese girl with CDG are reported. We also reviewed previous CDG cases that involved COG5 mutations by comparing the phenotypes and genotypes in different cases.ResultsThe patient was admitted to our hospital due to ataxia and psychomotor delay. The major clinical manifestations were postural instability, difficulty in walking, psychomotor delay, hypohidrosis, hyperkeratosis of the skin, and ulnar deviation of the right-hand fingers. Biochemical analyses revealed coagulation defect and liver lesions. Vision tests showed choroidopathy and macular hypoplasia. Whole-exome sequencing identified the hitherto unreported compound-heterozygous COG5 mutations, c.1290C > A (p.Y430X) and c.2077A > C (p.T693P). Mutation p.Y430X is nonsense, leading to a truncated protein. Mutation p.T693P is located at a highly conserved region, and thus the polar-to-non-polar substitution presumably affects the structure and function of COG5. According to the Human Genome Mutation Database Professional, there have been totally 13 CDG cases caused by 13 COG5 mutations. They are mainly characterized by psychomotor delay, hypotonia, ataxia, microcephaly, and hearing and visual abnormalities.ConclusionThe clinical manifestations of the patient are mild but consistent with the clinical characteristics of the published COG5-CDG cases. The results of this study extend the spectrum of clinical and genetic findings in COG5-CDG.

【 授权许可】

Unknown