[Genetics and hyperphenylalaninemias in 1992].
Hyperphenylalaninemias result from different enzymatic impairment, the most common and best studied which is phenylalanine hydroxylase (PAH) deficiency. The PAH gene has been cloned, sequenced and mapped: it is a single copy. Twenty-one mutations have now been characterized, but they constitute less than half of the haploid genotypes in French patients. A study of RFLP haplotypes is informative in 90% of families, but no linkage disequilibrium exists between illness and one particular haplotype. Prediction of phenotype from genotype seems possible, and could constitute a better therapeutic approach, perhaps including gene therapy in the most serious cases. The recently produced murine model should permit further progress to be made. Some hypotheses could be put forward about the origin and high frequency of this disease, that principally affects Caucasians: there is a consensus of opinion--though there is no definitive proof--that some selective advantage exists in individuals heterozygous for a PKU allele.
Service de pédiatrie-génétique, hôpital Debrousse, Lyon, France.
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Touraine
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Guibaud
D000293:Adolescent; D000328:Adult; D000368:Aged; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D015316:Genetic Therapy; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D010649:Phenylalanine / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D010651:Phenylalanine Hydroxylase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D010661:Phenylketonurias / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy
D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase
Génétique et hyperphénylalaninémies en 1992.