The novel transferrin E592A variant impairs the diagnostics of congenital disorders of glycosylation

Park, Julien H.; Zühlsdorf, Andrea; Wada, Yoshinao; Roll, Claudia; Rust, Stephan; Chesne, Ingrid Du; Grüneberg, Marianne; Marquardt, Thorsten

doi:10.1016/j.cca.2014.05.011

Cited by 11 publications

(7 citation statements)

References 10 publications

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“…Detailed N-glycan analysis of serum transferrin by electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS) was carried out, as described elsewhere. 24 ESI-TOF mass spectrometry of transferrin confirmed the loss of terminal sialic acids (Figure 3B, day 0). However, in addition to sialic acid, the majority of abnormal transferrin isoforms lacked one or more galactose residues, indicating a primary problem in galactosylation rather than sialylation (Figure 3B, day 0: G > F, E > D, C > B).…”

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confidence: 84%

SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation

Park

Hogrebe

Grüneberg

et al. 2015

The American Journal of Human Genetics

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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.

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confidence: 84%

SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation

Park

Hogrebe

Grüneberg

et al. 2015

The American Journal of Human Genetics

Self Cite

253

278

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“…Nano-electrospray Ionization Time-of-Flight Mass Spectrometry (nanoESI-TOF MS) NanoESI-TOF MS was performed as described previously by Park et al (2014).…”

Section: Immunoprecipitation and Sds-pagementioning

confidence: 99%

TMEM165 Deficiency: Postnatal Changes in Glycosylation

et al. 2015

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Congenital disorders of glycosylation form a rapidly growing group of inherited metabolic diseases. As glycosylation affects proteins all over the organism, a mutation in a single gene leads to a multisystemic disorder. We describe a patient with TMEM165-CDG with facial dysmorphism, nephrotic syndrome, cardiac defects, enlarged cerebral ventricles, feeding problems, and neurological involvement. Having confirmed the diagnosis via prenatal diagnostics, we were able to observe the glycosylation right from birth, finding a pathological pattern already on the first day of life. Within the next few weeks, hypoglycosylation progressed to less sialylated and then also to hypogalactosylated isoforms. On the whole, there has not been much published evidence concerning postnatal glycosylation and its adaptational process. This is the first paper reporting changes in glycosylation patterns over the first postnatal weeks in TMEM165-CDG.

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“…Before considering genetic testing, a secondary CDG, such as galactosemia and fructose intolerance, has to be excluded. 9,10 Genetic testing is often performed by analyzing a CDG gene panel. If this is normal, whole exome or whole genome sequencing should be the next step.…”

Section: Introductionmentioning

confidence: 99%

Ten years of screening for congenital disorders of glycosylation in Argentina: case studies and pitfalls

et al. 2018

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BACKGROUND: Congenital Disorders of Glycosylation (CDG) are genetic diseases caused by hypoglycosylation of glycoproteins and glycolipids. Most CDG are multisystem disorders with mild to severe involvement. METHODS: We studied 554 patients (2007-2017) with a clinical phenotype compatible with a CDG. Screening was performed by serum transferrin isoelectric focusing. The diagnosis was confirmed by genetic testing (Sanger or exome sequencing). RESULTS: A confirmed abnormal pattern was found in nine patients. Seven patients showed a type 1 pattern: four with PMM2-CDG, two with ALG2-CDG, and one with classical galactosemia. A type 2 pattern was found in two patients: one with a CDG-IIx and one with a transferrin protein variant. Abnormal transferrin pattern were observed in a patient with a myopathy due to a COL6A2 gene variant. CONCLUSIONS: CDG screening in Argentina from 2007 to 2017 revealed 4 PMM2-CDG patients, 2 ALG2-CDG patients with a novel homozygous gene variant and 1 CDG-IIx.

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The novel transferrin E592A variant impairs the diagnostics of congenital disorders of glycosylation

Cited by 11 publications

References 10 publications

SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation

SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation

TMEM165 Deficiency: Postnatal Changes in Glycosylation

Ten years of screening for congenital disorders of glycosylation in Argentina: case studies and pitfalls

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