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A heterozygous mutation in GOT1 is associated with familial macro-aspartate aminotransferase
- Source :
- Journal of hepatology. 67(5)
- Publication Year :
- 2017
-
Abstract
- Background & Aims Macro-aspartate aminotransferase (macro-AST) manifests as a persistent elevation of AST levels, because of association of the protein with immunoglobulins in the circulation. Macro-AST is a rare, benign condition without a previously confirmed genetic basis. Methods Whole exome sequencing (WES)-based screening was performed on 32 participants with suspected familial macro-AST, while validation of variants was performed on an extended cohort of 92 probands and 1,644 healthy controls using Taqman genotyping. Results A missense variant (p.Gln208Glu, rs374966349) in glutamate oxaloacetate transaminase 1 (GOT1) was found, as a putative causal variant predisposing to familial macro-AST. The GOT1 p.Gln208Glu mutation was detected in 50 (54.3%) of 92 probands from 20 of 29 (69%) families, while its prevalence in healthy controls was only 0.18%. In silico analysis demonstrated that the amino acid at this position is not conserved among different species and that, functionally, a negatively charged glutamate on the GOT1 surface could strongly anchor serum immunoglobulins. Conclusions Our data highlight that testing for the p.Gln208Glu genetic variant may be useful in diagnosis of macro-AST. Lay summary Higher than normal levels of aspartate aminotransferase (AST) in the bloodstream may be a sign of a health problem. Individuals with macro-AST have elevated blood AST levels, without ongoing disease and often undergo unnecessary medical tests before the diagnosis of macro-AST is established. We found a genetic variant in the GOT1 gene associated with macro-AST. Genetic testing for this variant may aid diagnosis of macro-AST.
- Subjects :
- 0301 basic medicine
Proband
Male
Disease
medicine.disease_cause
digestive system
Polymorphism, Single Nucleotide
03 medical and health sciences
0302 clinical medicine
medicine
Missense mutation
Humans
Genetic Predisposition to Disease
Aspartate Aminotransferases
Child
Genotyping
Exome sequencing
Genetic testing
Genetics
Mutation
Hepatology
medicine.diagnostic_test
biology
nutritional and metabolic diseases
digestive system diseases
stomatognathic diseases
030104 developmental biology
biology.protein
030211 gastroenterology & hepatology
Female
Antibody
Aspartate Aminotransferase, Cytoplasmic
Metabolism, Inborn Errors
Subjects
Details
- ISSN :
- 16000641
- Volume :
- 67
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of hepatology
- Accession number :
- edsair.doi.dedup.....8f84b6b5840d80b22b7fb57c6ee7d839