Mutation analysis in adenylosuccinate lyase deficiency: Eight novel mutations in the re-evaluated full ADSL coding sequence

The deficiency of adenylosuccinate lyase (ADSL, also termed adenylosuccinas e) is an autosomal recessive disorder characterized by the accumulation in body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Most ADSL deficient children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present. Up to now nine m issense mutations of the ADSL gene had been reported in six apparently unre lated sibships. In the present study of 10 additional patients with ADSL de ficiency, nine point mutations, among which seven unreported missense mutat ions, and the first splicing error reported in this disorder, have been ide ntified. These mutations have been characterized, taking into account the f inding that the cDNA of human ADSL is 75 nucleotides longer at its 5'-end, and encodes a protein of 484 rather than 459 amino acids as previously repo rted, Five apparently unrelated patients were found to carry a R426H mutati on. With the exceptions of the latter mutation, of a R190Q mutation that ha d been reported previously and of a K246E mutation that was found in two un related patients, all other mutations were found only in a single family. H um Mutat 13:197-202, 1999. (C) 1999 Wiley-Liss, Inc.