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SLC35A2-CDG: Novel variant and review.
Dulce Quelhas1,2,3, Joana Correia3, Jaak Jaeken4
1Unidade de Bioquímica Genética, Centro de Genética Médica Jacinto de Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal.
Molecular Genetics and Metabolism Reports
|February 8, 2021
Summary
Congenital disorder of glycosylation (CDG) due to SLC35A2 variants typically affects males severely. This study reports a novel SLC35A2 variant in a male with milder symptoms, suggesting a broader clinical spectrum.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- The SLC35A2 gene encodes a transporter crucial for glycosylation, moving uridine diphosphate (UDP)-galactose into the Golgi apparatus.
- Pathogenic variants in SLC35A2 cause a congenital disorder of glycosylation (CDG) predominantly affecting males, often presenting with severe epileptic encephalopathy.
Observation:
- This review details a male patient with SLC35A2-CDG exhibiting growth deficiency, decreased serum IGF1, mild neurological and facial features, and camptodactyly, notably without epilepsy.
- Genetic analysis identified a novel de novo hemizygous variant, c.233A>G (p.Lys78Arg), in the SLC35A2 gene.
Findings:
- Sequence analysis revealed that the identified variant and other reported pathogenic mutations occur at conserved positions within SLC35A2 and its paralogs (SLC35A1, SLC35A3).
- This conservation suggests critical functional importance, explaining the severe pathological effects of mutations at these sites.
Implications:
- The findings expand the known clinical spectrum of SLC35A2-CDG, indicating that not all pathogenic variants lead to severe epileptic encephalopathy.
- The conservation data provides strong evidence for the pathogenicity of mutations at specific residues and may help explain the observed gender bias in SLC35A2-CDG patients.
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