The extent to which non-coding mutations contribute to Mendelian disease is a major unknown in human genetics. Relatedly, the vast majority of candidate regulatory elements have yet to be functionally validated. Here, we describe a CRISPR-based system that uses pairs of guide RNAs (gRNAs) to program thousands of kilobase-scale deletions that deeply scan across a targeted region in a tiling fash...

2003;21:401–7. 6. Ensenauer R, Muller CB, Schwab KO, Gibson KM, Brandis M, Lehnert W. 3-Methylglutaconyl-CoA hydratase deficiency: a new patient with speech retardation as the leading sign. J Inherit Metab Dis 2000;23:341–4. 7. Hou JW, Wang TR. 3-Methylglutaconic aciduria presenting as Reye syndrome in a Chinese boy. J Inherit Metab Dis 1995;18:645–6. 8. Jooste S, Erasmus E, Mienie LJ, de Wet W...

BACKGROUND Lesch-Nyhan disease is an inborn error of purine metabolism that results from deficiency of the activity of hypoxanthine phosphoribosyltransferase (HPRT). In the classic disease, the activity of the enzyme is completely deficient; the patient has mental retardation, spasticity, dystonia, and self-injurious behavior, as well as elevated concentrations of uric acid in blood and urine a...

Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), an enzyme encoded by the HPRT1 gene. The classic disease phenotype described by Lesch and Nyhan in 1964 includes hyperuricemia, mental retardation, severe motor deficiency, and recurring self-mutilation. Here, we report the case of a family with 4 affecte...

Certain gouty subjects with excessive de novo purine synthesis are deficient in hypoxanthineguanine phosphoribosyltransferase (HG-PRTase [EC 2.4.2.8]). The mechanism of accelerated uric acid formation in these patients was explored by measuring the incorporation of glycine-(14)C into various urinary purine bases of normal and enzyme-deficient subjects during treatment with the xanthine oxidase ...