Novel compound heterozygous COG5 mutations in a Chinese male patient with severe clinical symptoms and type�IIi congenital disorder of glycosylation: A case report

Abstract

In the current study, one case of COG5-CDG involving a Chinese male patient with severe neurological symptoms, who had previously been misdiagnosed with congenital gyrus malformation, is described. A clinical investigation was performed and targeted next-generation sequencing (NGS) was used to identify COG5 variants in the patient and his family. PCR and Sanger sequencing were performed for the verification of NGS results. The patient showed severe central and peripheral neurological symptoms, while only mild symptoms were reported in a previous reported case, in which different mutations were involved. The reported patient carried the frameshift mutation c.330delT (p.V111Lfs * 22), and a missense mutation c.2324 C>T (p.P775L) in the COG5 gene. The c.330delT (p.V111Lfs * 22) variant is a novel mutation, while c.2324 C>T (p.P775L) has previously been reported. Inheriting one variant from each of his parents, the current case report furthers the understanding of genotype-phenotype correlations in COG5-CDG.

Golgi inCOGnito: From vesicle tethering to human disease

“… Truncated p.V111Lfs*22 (by 690aa) non- functional – Most severe COG5-CDG phenotype including severe mental retardation, delayed speech and motor development, microcephaly, cerebral and cerebellar atrophy, hypotonia, recurrent seizures, liver involvement and small feet. [ 96 ] Heterozygous c.1290C > A (p.Y430X) c.2077A > C (p.T693P) T693 is highly conserved 80% depletion of WT COG5. Truncated COG5 present at very low levels – Neonatal jaundice, recurrent upper respiratory tract infections, hypohidrosis, hyperkeratosis, ulnar deviation and delayed psychomotor development.…”

“…Unlike the previous COG5-CDG cases, these siblings did not have hypotonia, microcephaly and short stature. In 2019, Yin et al [ 96 ] described a COG5-CDG patient (P7) with smaller feet and liver involvement in addition to severe neurological involvement such as mental retardation, delayed motor and speech development, cerebral and cerebellar atrophy, microcephaly, hypotonia and recurrent seizures.…”

“…Truncated COG5 was also expressed at low levels. P8 [ 96 ] was heterozygous for a missense mutation c.2324C > T (p.P775L) gene and a novel frameshift mutation c.330delT (p.V111Lfs*22) in the COG5 gene, each inherited from one parent. The author believes that these COG5 compound heterozygous mutations may cause glycosylation defects like other COG5-CDG.…”

Quality control of protein complex assembly by the ubiquitin–proteasome system

“…The conserved oligomeric Golgi (COG) complex is a ~500 kDa tethering complex that coordinates retrograde vesicle trafficking within the Golgi [32,33]. Defects in the COG complex affect the cellular glycosylation balance, and mutations in COG subunits result in congenital glycosylation disorders [34][35][36][37]. COG is composed of eight subunits, COG1-8, which are arranged into a bilobed structure in which the two lobes are composed of subunits COG2/3/4 and COG5/6/7, respectively [32,33].…”