Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in <i>GLS</i>.

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 o

SUBMITTER: van Kuilenburg ABP 

PROVIDER: S-EPMC8819703 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature