Date of Award

5-2022

Document Type

Thesis - Closed Access

Degree Name

MS in Human Genetics

First Advisor

Claire Davis

Abstract

Congenital disorders of glycosylation (CDGs) are a rare group of genetic metabolic disorders characterized by defective glycoprotein biosynthesis. Given the prevalence of glycosylation pathways throughout the body, CDGs are considered multi-system disorders with a wide spectrum of clinical features. In this report, we present a patient with a clinical and biochemical diagnosis of SLC39A8-CDG but with only one identifiable coding variant in SLC39A8. A second heterozygous intronic variant of uncertain significance was identified by Whole Genome Sequencing (WGS). In comparison to previously reported cases of SLC39A8-CDG, our proband has a mild presentation with less severe developmental delay, motor disability and brain abnormalities. To date, we are aware of two other cases (not reported here) where the patients are biochemically diagnosed with CDG IIn but, similarly, WES was only able to identify one coding variant. This raises the possibility that missing heritability/noncoding variants could be prevalent in this condition and it may be necessary to conduct further genome research to explore the role of noncoding variants in this metabolic disorder.

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