Alternative titles; symbols
SNOMEDCT: 718751000; ORPHA: 263501; DO: 0070262;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 16q22.1 | Congenital disorder of glycosylation, type IIj | 613489 | Autosomal recessive | 3 | COG4 | 606976 |
A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type IIj (CDG IIj, CDG2J) is caused by compound heterozygous mutation in the COG4 gene (606976) on chromosome 16q22.
For a general discussion of CDGs, see CDG1A (212065).
Reynders et al. (2009) reported a Portuguese boy, born of unrelated parents, with CDG type II. He presented at age 4 months with fever, progressive irritability, and complex seizures after a vaccination. He had mild dysmorphic features, such as down-sloping frontal area and thick hair, as well as mild neurologic signs, including axial hypotonia, mild peripheral hypertonia, and hyperreflexia. Laboratory studies showed increased serum transaminases, alkaline phosphatase, and LDH cholesterol, but decreased platelet count and coagulation factors. Isoelectric focusing of serum transferrin showed a type 2 pattern. The patient later developed recurrent respiratory infections. By age 3 years, he had microcephaly, cerebral atrophy of the frontotemporal regions, ataxia, absence of speech, and moderate psychomotor retardation. Reynders et al. (2009) noted that the phenotype in this patient was not as severe as that observed in patients with type II CDG due to other COG defects, including CDG2G (611209), CDG2E (608779), and CDG2H (611182). The clinical severity of these phenotypes correlated with structural and biochemical abnormalities of the Golgi complex, with the COG4 mutant being the mildest.
Ng et al. (2011) reported an Indian child with a severe form of CDG2J, who had originally been reported by Miura et al. (2005). He had failure to thrive in infancy with recurrent diarrhea. He also had recurrent respiratory and gastrointestinal infections with sepsis and hypotensive shock at age 11 months. Other features included profound developmental delay, hypotonia, nystagmus, hepatosplenomegaly, and poor growth. Brain MRI showed diffuse cerebral atrophy and thinning of the corpus callosum. Seizures developed occurred at age 16 months. The course was progressive, and he developed liver cirrhosis, coagulopathy, and recurrent infections that were ultimately fatal around age 2 years. The patient had 2 unaffected sibs. Patient serum N-glycans showed deficiencies in both sialylation and galactosylation, and patient fibroblasts showed impaired O-glycosylation, indicating a combined deficiency. Patient fibroblasts also showed a defect in Brefeldin A (BFA)-induced retrograde transport of Golgi proteins back to the endoplasmic reticulum. Ng et al. (2011) noted the more severe phenotype compared to that reported by Reynders et al. (2009).
The transmission pattern of CDG2J in the families reported by Reynders et al. (2009) and Ng et al. (2011) was consistent with autosomal recessive inheritance.
Reynders et al. (2009) reported a Portuguese patient with congenital disorder of glycosylation type IIj and identified compound heterozygosity for a missense mutation in the COG4 gene and a large deletion encompassing most COG4 exons (606976.0001-606976.0002, respectively).
In an Indian patient, born of unrelated parents, with a severe form of CDG2J, Ng et al. (2011) identified compound heterozygous mutations in the COG4 gene (606976.0003 and 606976.0004). There was an isolated reduction in COG4 protein expression.
Miura, Y., Tay, S. K. H., Aw, M. M., Eklund, E. A., Freeze, H. H. Clinical and biochemical characterization of a patient with congenital disorder of glycosylation (CDG) IIX. J. Pediat. 147: 851-853, 2005. [PubMed: 16356446] [Full Text: https://doi.org/10.1016/j.jpeds.2005.07.038]
Ng, B. G., Sharma, V., Sun, L., Loh, E., Hong, W., Tay, S. K. H., Freeze, H. H. Identification of the first COG-CDG patient of Indian origin. Molec. Genet. Metab. 102: 364-367, 2011. [PubMed: 21185756] [Full Text: https://doi.org/10.1016/j.ymgme.2010.11.161]
Reynders, E., Foulquier, F., Teles, E. L., Quelhas, D., Morelle, W., Rabouille, C., Annaert, W., Matthijs, G. Golgi function and dysfunction in the first COG4-deficient CDG type II patient. Hum. Molec. Genet. 18: 3244-3256, 2009. [PubMed: 19494034] [Full Text: https://doi.org/10.1093/hmg/ddp262]