title: HPRT deficiency: identification of twenty-four novel variants including an unusual deep intronic mutation.
abstract: Hypoxanthine phosphoribosyltranferase (HPRT) deficiency is an X-linked disorder of purine salvage that ranges phenotypically from hyperuricaemia to Lesch-Nyhan Syndrome. Molecular testing is necessary to identify female carriers within families as a prelude to prenatal diagnosis. During the period 1999-2010 the Purine Research Laboratory studied 106 patients from 68 different families. Genomic sequencing revealed mutations in 88% of these families, 24 of which were novel. In eight patients, exon sequencing was not informative. Copy-DNA analysis in one patient revealed an insertion derived from a deep intronic sequence with a genomic mutation flanking this region, resulting in the creation of a false exon. Carrier testing was performed in 21 mothers of affected patients, out of these, 81% (17) were found to be carriers of the disease-associated mutation. Our results confirm the extraordinary variety and complexity of mutations in HPRT deficiency. A combination of genomic and cDNA sequencing may be necessary to define mutations.
authors: Purine Research Laboratory, GSTS Pathology, London, UK.
authors: A
authors: A
authors: Corrigan
authors: M
authors: M
authors: Arenas
authors: E
authors: E
authors: Escuredo
authors: L
authors: L
authors: Fairbanks
authors: A
authors: A
authors: Marinaki
mesh_terms: D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase