Mechanisms for phenotypic variation in Lesch-Nyhan disease and its variants

SAMPAT R; FU R; LAROVERE LE; TORRES RJ; CEBALLOS-PICOT I; FISCHBACH M; DE KREMER R; SCHRETLEN DJ; PUIG JG; JINNAH HA

SPRINGER

Lugar: Berlín; Año: 2011 vol. 129 p. 71 - 71

esch-Nyhan disease is a neurogenetic disorder caused by mutation of the HPRT1 gene on the X chromosome.There is signiWcant variation in the clinical phenotype, with more than 300 diVerent known mutations. There are few studies that have addressed whether similar mutations result in similar phenotypes across diVerent patients because hypoxanthine-guanine phosphoribosyltransferase (HGprt) deWciency is rare, and most mutations are unique or limited to individual families. However, recent studies have revealed multiple unrelated patients with similar mutations, providing an opportunity to examine genotype?phenotype correlations. We found signiWcant variation among the clinical features of 10 patients from 8 unrelated families all carrying a mutation replacing guanine with adenine at base position 143 (c.143G>A) in the HPRT1 gene. This mutation results in replacement of arginine by histidine at amino acid position 48 (p.arg48his) in the HGprt enzyme. Biochemically, the enzyme e