학술논문
Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS.
Document Type
Article
Author
Leen, R.; Koster, J.; Meijer, J.; Tseng, L. A.; Turkenburg, M.; van Weeghel, M.; van Kuilenburg, A. B. P.; Wanders, R. J. A.; Waterham, H. R.; van Karnebeek, C. D. M.; Doizhenko, E.; Eberle, M. A.; Hayward, B.; Kumari, D.; Usdin, K.; Jones, M. J.; Kobor, M. S.; Geraghty, M. T.; McDonald, C.; Rajan-Babu, l. S.
Source
Subject
*MICROSATELLITE repeats
*INBORN errors of metabolism
*MESSENGER RNA
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Language
ISSN
0028-4793
Abstract
We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5' untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing. [ABSTRACT FROM AUTHOR]