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A novel homozygous mutation in the human ALG12 gene results in an aberrant profile of oligomannose N‐glycans in patient's serum
Author(s) -
Ziburová Jana,
Nemčovič Marek,
Šesták Sergej,
Bellová Jana,
Pakanová Zuzana,
Siváková Barbara,
Šalingová Anna,
Šebová Claudia,
Ostrožlíková Mária,
Lekka DimitraEvanthia,
Brucknerová Jana,
Brucknerová Ingrid,
Skokňová Martina,
Mc Cullough Alexandra,
Hrčková Gabriela,
Hlavatá Anna,
Bzdúch Vladimír,
Mucha Ján,
Baráth Peter
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62474
Subject(s) - exon , glycosylation , compound heterozygosity , gene , mutation , transferrin , glycan , ovotransferrin , biology , genetics , microbiology and biotechnology , medicine , glycoprotein , endocrinology
Congenital disorder of glycosylation type Ig (ALG12‐CDG) is a rare inherited metabolic disease caused by a defect in alpha‐mannosyltransferase 8, encoded by the ALG12 gene (22q13.33). To date, only 15 patients have been diagnosed with ALG12‐CDG globally. Due to a newborn Slovak patient's clinical and biochemical abnormalities, the isoelectric focusing of transferrin was performed with observed significant hypoglycosylation typical of CDG I. Furthermore, analysis of neutral serum N‐glycans by mass spectrometry revealed the accumulation of GlcNAc2Man5–7 and decreased levels of GlcNAc2Man8–9, which indicated impaired ALG12 enzymatic activity. Genetic analysis of the coding regions of the ALG12 gene of the patient revealed a novel homozygous substitution mutation c.1439T>C p.(Leu480Pro) within Exon 10. Furthermore, both of the patient's parents and his twin sister were asymptomatic heterozygous carriers of the variant. This comprehensive genomic and glycomic approach led to the confirmation of the ALG12 pathogenic variant responsible for the clinical manifestation of the disorder in the patient described.