| Literature DB >> 26637979 |
Julien H Park1, Max Hogrebe1, Marianne Grüneberg1, Ingrid DuChesne1, Ava L von der Heiden1, Janine Reunert1, Karl P Schlingmann1, Kym M Boycott2, Chandree L Beaulieu2, Aziz A Mhanni3, A Micheil Innes4, Konstanze Hörtnagel5, Saskia Biskup5, Eva M Gleixner5, Gerhard Kurlemann1, Barbara Fiedler1, Heymut Omran1, Frank Rutsch1, Yoshinao Wada6, Konstantinos Tsiakas7, René Santer7, Daniel W Nebert8, Stephan Rust1, Thorsten Marquardt9.
Abstract
SLC39A8 is a membrane transporter responsible for manganese uptake into the cell. Via whole-exome sequencing, we studied a child that presented with cranial asymmetry, severe infantile spasms with hypsarrhythmia, and dysproportionate dwarfism. Analysis of transferrin glycosylation revealed severe dysglycosylation corresponding to a type II congenital disorder of glycosylation (CDG) and the blood manganese levels were below the detection limit. The variants c.112G>C (p.Gly38Arg) and c.1019T>A (p.Ile340Asn) were identified in SLC39A8. A second individual with the variants c.97G>A (p.Val33Met) and c.1004G>C (p.Ser335Thr) on the paternal allele and c.610G>T (p.Gly204Cys) on the maternal allele was identified among a group of unresolved case subjects with CDG. These data demonstrate that variants in SLC39A8 impair the function of manganese-dependent enzymes, most notably β-1,4-galactosyltransferase, a Golgi enzyme essential for biosynthesis of the carbohydrate part of glycoproteins. Impaired galactosylation leads to a severe disorder with deformed skull, severe seizures, short limbs, profound psychomotor retardation, and hearing loss. Oral galactose supplementation is a treatment option and results in complete normalization of glycosylation. SLC39A8 deficiency links a trace element deficiency with inherited glycosylation disorders.Entities:
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Year: 2015 PMID： 26637979 PMCID： PMC4678430 DOI： 10.1016/j.ajhg.2015.11.003
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025