Molecular analysis of HPRT1(+) somatic cell hybrids derived from a carrier of an HPRT1 mutation responsible for Lesch-Nyhan syndrome.
Heterozygous carriers of HPRT1 mutations responsible for Lesch-Nyhan syndrome can be detected by analysis of somatic cell hybrids derived from peripheral blood lymphocytes and Hprt1-negative cells of rodent origin followed by selection in culture medium containing hypoxanthine, aminopterine, and thymidine (HAT). The parental origin of the X chromosome containing the normal HPRT1 allele in HPRT1(+) hybrid cell lines can be determined by molecular haplotyping attributable to highly polymorphic X-linked markers. We used this procedure to study a presumed carrier whose paternal active X chromosome always segregated in the cell hybrids derived from her. Conversely, her maternal X chromosome was systematically absent in most cell hybrids, or when present, it was inactive and coexisted with an active, paternal X chromosome. These results clearly demonstrated that the proband was a heterozygous carrier of a mutation responsible for HPRT1 deficiency.
Rivero
M B
MB
Divisão de Genética, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Olicio
R
R
Lima
C R
CR
Bonvicino
C R
CR
Moreira
M A
MA
Llerena
J C
JC
Seuánez
H N
HN
D000328:Adult; D000818:Animals; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D006822:Hybrid Cells; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics*; D007926:Lesch-Nyhan Syndrome / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D014960:X Chromosome / Q000235:genetics
D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase