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Mutation analysis in adenylosuccinate lyase deficiency: Eight novel mutations in the re‐evaluated full ADSL coding sequence
Author(s) -
Marie Sandrine,
Cuppens Harry,
Heuterspreute Michel,
Jaspers Martine,
Tola Eduardo Zambrano,
Gu Xiao Xiao,
Legius Eric,
Vincent M.Françoise,
Jaeken Jaak,
Cassiman JeanJacques,
Van den Berghe Georges
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1999)13:3<197::aid-humu3>3.0.co;2-d
Subject(s) - biology , missense mutation , genetics , mutation , point mutation , psychomotor retardation , gene , medicine , alternative medicine , pathology
The deficiency of adenylosuccinate lyase (ADSL, also termed adenylosuccinase) 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 missense mutations of the ADSL gene had been reported in six apparently unrelated sibships. In the present study of 10 additional patients with ADSL deficiency, nine point mutations, among which seven unreported missense mutations, and the first splicing error reported in this disorder, have been identified. These mutations have been characterized, taking into account the finding 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 reported. Five apparently unrelated patients were found to carry a R426H mutation. With the exceptions of the latter mutation, of a R190Q mutation that had been reported previously, and of a K246E mutation that was found in two unrelated patients, all other mutations were found only in a single family. Hum Mutat 13:197–202, 1999. © 1999 Wiley‐Liss, Inc.