The early development of self-injurious behaviour in three young boys (aged 17, 25, and 30 months at start of study) with Lesch-Nyhan syndrome was examined by means of parental interviews and by direct observations completed at 3 to 4 monthly intervals over an 18-month period. Results suggest that the self-injury began in a different way from that of other young children with autism and/or deve...

Watts, R. W. E., McKeran, R. O., Brown, E., Andrews, T. M., and Griffiths, M. I. (1974). Archives of Disease in Childhood, 49, 693. Clinical and biochemical studies on treatment of Lesch-Nyhan syndrome. The clinical findings in a previously unreported case of the Lesch-Nyhan syndrome are described. Though formal intellectual testing is very difficult because of the severe choreoathetosis and co...

Lesch-Nyhan disease (LND) is a rare inherited disorder caused by mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT). LND is characterized by overproduction of uric acid, leading to gouty arthritis and nephrolithiasis. Affected patients also have characteristic neurological and behavioral anomalies. Multiple cell models have been developed to study the molecular...

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...

The spectral flow is a well-known quantity in theory that measures the variation of spectra about 0 along paths selfadjoint Fredholm operators. aim this work twofold. Firstly, we consider homotopy invariance properties and establish simple formula which comprises its classical yields comparison theorem for under compact perturbations. We apply our result to existence non-trivial solutions bound...

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is pr...