Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in .

08:00 EDT 11th April 2019 | BioPortfolio

Summary of "Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in ."

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 () 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 messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the 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.


Journal Details

This article was published in the following journal.

Name: The New England journal of medicine
ISSN: 1533-4406
Pages: 1433-1441


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Medical and Biotech [MESH] Definitions

Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (INVERTED TANDEM REPEATS).

Tandem arrays of moderately repetitive (5-50 repeats) short (10-60 bases) DNA sequences found dispersed throughout the genome and clustered near telomeres. Their degree of repetition is two to several hundred at each locus. Loci number in the thousands but each locus shows a distinctive repeat unit. Minisatellite repeats are often called variable number of tandem repeats.

An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.

A variety of simple di- (DINUCLEOTIDE REPEATS), tri- (TRINUCLEOTIDE REPEATS), tetra-, and pentanucleotide tandem repeats (usually less than 100 bases long). They are dispersed in the euchromatic arms of most chromosomes. They are also known as short tandem repeats (STRs).

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