| Autor: |
H, Kodera, N, Ando, I, Yuasa, Y, Wada, Y, Tsurusaki, M, Nakashima, N, Miyake, S, Saitoh, N, Matsumoto, H, Saitsu |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
Clinical genetics. 87(5) |
| ISSN: |
1399-0004 |
| Popis: |
The conserved oligomeric Golgi (COG) complex is involved in intra-Golgi retrograde trafficking, and mutations in six of its eight subunits have been reported in congenital disorders of glycosylation (CDG). Here we report a patient showing severe acquired microcephaly, psychomotor retardation, seizures, liver dysfunction, hypocupremia, and hypoceruloplasminemia. Analysis of his serum glycoproteins revealed defects in both sialylation and galactosylation of glycan termini. Trio-based whole-exome sequencing identified two heterozygous mutations in COG2: a de novo frameshift mutation [c.701dup (p.Tyr234*)] and a missense mutation [c.1900T G (p.Trp634Gly)]. Sequencing of cloned reverse-transcription polymerase chain reaction (RT-PCR) products revealed that both mutations were located on separate alleles, as expected, and that the mutant transcript harboring the frameshift mutation underwent degradation. The c.1900T G (p.Trp634Gly) mutation is located in a domain highly conserved among vertebrates and was absent from both the public database and our control exomes. Protein expression of COG2, along with COG3 and COG4, was decreased in fibroblasts from the patient. Our data strongly suggest that these compound heterozygous mutations in COG2 are causative of CDG. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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