SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation
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SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation. / Park, Julien H; Hogrebe, Max; Grüneberg, Marianne; DuChesne, Ingrid; von der Heiden, Ava L; Reunert, Janine; Schlingmann, Karl P; Boycott, Kym M; Beaulieu, Chandree L; Mhanni, Aziz A; Innes, A Micheil; Hörtnagel, Konstanze; Biskup, Saskia; Gleixner, Eva M; Kurlemann, Gerhard; Fiedler, Barbara; Omran, Heymut; Rutsch, Frank; Wada, Yoshinao; Tsiakas, Konstantinos; Santer, René; Nebert, Daniel W; Rust, Stephan; Marquardt, Thorsten.
in: AM J HUM GENET, Jahrgang 97, Nr. 6, 03.12.2015, S. 894-903.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation
AU - Park, Julien H
AU - Hogrebe, Max
AU - Grüneberg, Marianne
AU - DuChesne, Ingrid
AU - von der Heiden, Ava L
AU - Reunert, Janine
AU - Schlingmann, Karl P
AU - Boycott, Kym M
AU - Beaulieu, Chandree L
AU - Mhanni, Aziz A
AU - Innes, A Micheil
AU - Hörtnagel, Konstanze
AU - Biskup, Saskia
AU - Gleixner, Eva M
AU - Kurlemann, Gerhard
AU - Fiedler, Barbara
AU - Omran, Heymut
AU - Rutsch, Frank
AU - Wada, Yoshinao
AU - Tsiakas, Konstantinos
AU - Santer, René
AU - Nebert, Daniel W
AU - Rust, Stephan
AU - Marquardt, Thorsten
N1 - Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
PY - 2015/12/3
Y1 - 2015/12/3
N2 - 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.
AB - 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.
U2 - 10.1016/j.ajhg.2015.11.003
DO - 10.1016/j.ajhg.2015.11.003
M3 - SCORING: Journal article
C2 - 26637979
VL - 97
SP - 894
EP - 903
JO - AM J HUM GENET
JF - AM J HUM GENET
SN - 0002-9297
IS - 6
ER -