Novel mutation of COG5 in a Taiwanese girl with congenital disorders of glycosylation manifesting as developmental delay

Abstract

We are documenting the case of An 11-year-old girl who has been followed up at our out-patient clinic since birth with clinical presentations including intrauterine growth restriction, recurrent periodic fever in infancy, hypotonia, global developmental delay, liver function impairment with cirrhotic changes, and clinodactyly. Congenital abnormalities were suspected but a series of examinations including brain MRI, liver biopsy and muscle biopsy yielded insignificant findings. Whole genome sequencing (WGS) was conducted and revealed three novel mutations (c2T > G, c1826T > C, c.556-560delAGTAAinsCT) of the COG5 gene. A diagnosis of COG5-congenital disorders of glycosylation (COG5-CDG, or CDG IIi), with neurologic presentation was established. Sanger sequencing in the patient and her parents confirmed the compound heterozygous mutation. Upon literature review, we identified the patient as the first case of COG5-CDG in Taiwan. Our study enhances the clarity of the correlation between the mutative genes and the presentation of COG5-CDG.

Keywords: COG5; Congenital disorders of glycosylation; Developmental delay.

Fig. 1

Photos of the patient and analysis of the genetic data A. Front photograph of the patient. B. Left side photograph of the patient. C. Left hand photograph of the patient. D. Right hand photograph of the patient. E. Photograph of the patient's feet. F. Right foot photograph of the patient. G. Left foot photograph of the patient. H. Pedigree of the patient. I. Sanger sequencing of the patient and her parents.

Fig. 2

Magnetic Resonance Imaging of Brain of the patient. A&B. Magnetic Resonance Spectroscopy done when the patient was 14 months old showed some degree of demyelinating process in the white matter and presence of gliosis could not be excluded. C. Magnetic Resonance Imaging of Brain followed up when the patient was 6 years and 9 months old showed bilateral smaller optic tracts, indicating congenital hypoplasia.

Fig. 3

Electron microscopic images of the patient's muscle biopsy. A&B. Muscle biopsy done when the patient was 16 months old, showed the vesicles full of glycogens aggregate in the cytoplasm of the skeletal muscle cells.