| Literature DB >> 30970188 |
André B P van Kuilenburg1, Maja Tarailo-Graovac1, Phillip A Richmond1, Britt I Drögemöller1, Mahmoud A Pouladi1, René Leen1, Koroboshka Brand-Arzamendi1, Doreen Dobritzsch1, Egor Dolzhenko1, Michael A Eberle1, Bruce Hayward1, Meaghan J Jones1, Farhad Karbassi1, Michael S Kobor1, Janet Koster1, Daman Kumari1, Meng Li1, Julia MacIsaac1, Cassandra McDonald1, Judith Meijer1, Charlotte Nguyen1, Indhu-Shree Rajan-Babu1, Stephen W Scherer1, Bernice Sim1, Brett Trost1, Laura A Tseng1, Marjolein Turkenburg1, Joke J F A van Vugt1, Jan H Veldink1, Jagdeep S Walia1, Youdong Wang1, Michel van Weeghel1, Galen E B Wright1, Xiaohong Xu1, Ryan K C Yuen1, Jinqiu Zhang1, Colin J Ross1, Wyeth W Wasserman1, Michael T Geraghty1, Saikat Santra1, Ronald J A Wanders1, Xiao-Yan Wen1, Hans R Waterham1, Karen Usdin1, Clara D M van Karnebeek1.
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.Entities:
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Year: 2019 PMID： 30970188 PMCID： PMC8819703 DOI： 10.1056/NEJMoa1806627
Source DB: PubMed Journal: N Engl J Med ISSN： 0028-4793 Impact factor: 91.245