Abstract
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.
Highlights
Congenital Disorders of Glycosylation (CDGs) represent a group of metabolic disorders resulting from defects in the glycosylation of proteins
Pattern visual evoked potential (PVEP) test revealed that the latencies of P100 waves at 1-degree checks were roughly normal but the P100 amplitudes were moderately reduced in both eyes; the latencies at 0.25-degree checks were significantly longer, and the amplitudes were severely reduced in both eyes, suggesting choroiditis in the retina and hypoplasia in the macula lutea (Figure 2C)
COG5CDG is a subtype of CDG II, affecting modification pathways of N-linked oligosaccharide (Sparks and Krasnewich, 2017)
Summary
Congenital Disorders of Glycosylation (CDGs) represent a group of metabolic disorders resulting from defects in the glycosylation of proteins. Most of CDGs are autosomal recessive, but autosomal dominant and X-linked ones have been reported. The classification of CDGs depend on the defective enzyme and its function. More than 130 types of CDGs characterized to date involve. Two Novel Mutations in COG5-CDG enzymes participating in various steps along glycosylation pathways (Chang et al, 2018). The deficiency of COG5 leads to COG5-CDG, which is a rare type and usually caused by mutations in the COG5 gene. 7 of 13 cases have provided clinical information in detail to date. We report a 4-year-old Chinese patient carrying two novel compound-heterozygous mutations in COG5, whereby we expand the mutation database
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