γ-glutamyl transpeptidase deficiency caused by a large homozygous intragenic deletion in GGT1

European Journal of Human Genetics : EJHG
Niklas DarinJorge Asin-Cayuela

Abstract

γ-Glutamyl transpeptidase deficiency (glutathionuria, OMIM 231950) is a rare disease, with only six patients reported in the literature, although this condition has probably been underdiagnosed due the difficulty to routinely analyze glutathione in clinical samples and to the fact that no genetic defect has been coupled to the disease so far. We report two siblings with mild psychomotor developmental delay and mild neurological symptoms, who presented a markedly increased excretion of glutathione in urine and a very low γ-glutamyl transpeptidase activity in serum. Whole-genome sequencing revealed the presence of a 16.9 kb homozygous deletion in GGT1, one of the genes encoding enzymes with γ-glutamyl transpeptidase activity in the human genome. Close analysis revealed the presence of a 13 bp insertion at the deletion junction. This is the first report of a genetic variant as the cause of glutathionuria. In addition, genetic characterization of the patients' parents and a healthy sibling has provided direct genetic evidence regarding the autosomal recessive nature of this disease.

References

Jul 8, 1975·Biochemical and Biophysical Research Communications·J D SchulmanE J Butler
Jan 1, 1990·Methods in Enzymology·J Ozols
Jan 30, 1971·Lancet·S I GoodmanS Pollack
Jun 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·O W Griffith, A Meister
Jan 1, 1980·Journal of Inherited Metabolic Disease·E C WrightA D Patrick
Jan 1, 1995·Journal of Inherited Metabolic Disease·J W HammondR Truscott
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·M W LiebermanM M Matzuk
Sep 26, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y WillD J Reed
Sep 6, 2002·Biochemical Pharmacology·Dale A Dickinson, Henry Jay Forman
Feb 11, 2005·Journal of Inherited Metabolic Disease·M IidaH Kubo
Mar 22, 2008·Human Genetics·Nora HeisterkampTam P Sneddon
Jan 27, 2009·Biological Chemistry·Nazzareno BallatoriChristine L Hammond
Mar 31, 2011·Analytical Biochemistry·Stephanie WickhamMarie H Hanigan
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Sep 24, 2013·Nature Genetics·Claudia M B CarvalhoJames R Lupski
Nov 5, 2014·Genes & Development·Ranjith P AnandJames E Haber
Apr 18, 2015·BMC Cancer·Timothy T BuiGordon Li
Mar 1, 2016·Nature Reviews. Genetics·Claudia M B Carvalho, James R Lupski

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Citations

Sep 15, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alessandro De GrandiAndreas R Janecke
Nov 2, 2019·Scientific Reports·C E T AraújoA S Borges
Apr 6, 2021·Current Opinion in Biotechnology·Gloria Asantewaa, Isaac S Harris
May 4, 2021·EMBO Molecular Medicine·Kalliopi SofouFredrik H Sterky

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Methods Mentioned

BETA
PCR
electrophoresis
ion-exchange chromatography

Software Mentioned

Ingenuity Variant Analysis
Integrative Genomics Viewer ( IGV )
CLC Biomedical Server
CLC Fixed Ploidy
IGV browser
ClustalO

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