TY - JOUR
T1 - POLYMORPHIC DNA HAPLOTYPES AT THE PHENYLALANINE HYDROXYLASE LOCUS IN PRENATAL DIAGNOSIS OF PHENYLKETONURIA
AU - Daiger, Stephen P.
AU - Chakraborty, Ranajit
AU - Güttler, Flemming
AU - Lidsky, Alan S.
AU - Koch, Richard
AU - Woo, Savio L.C.
N1 - Funding Information:
We thank Ms Susan Sullivan and Ms Sharon Moore for excellent technical assistance, Cathy Crowley, MS, RN, for obtaining blood samples, and Dr John Ymg for preparing the blood samples at the Children’s Hospital of Los Angeles. This research was supported in part by grants AM30471 and HD17711 from the National Institutes of Health, USA. S. L. C. W. is also an investigator of the Howard Hughes Medical Institute.
PY - 1986/2/1
Y1 - 1986/2/1
N2 - Restriction fragment length polymorphisms (RFLPs) detected in the human genome by means of a cDNA clone of phenylalanine hydroxylase (PAH) segregate concordantly with phenylketonuria (PKU) in several families. To establish the usefulness of these DNA polymorphisms for prenatal diagnosis of PKU the genotypes and chromosomal haplotypes of eight RFLPs at the PAH locus were determined in 46 families, each with one or more affected children. 34 of these families were informative for linkage analysis, giving a maximum probability of 109:1 in favour of tight linkage between PKU and the PAH RFLP haplotypes. Thus the deficiency of hepatic PAH in PKU patients is caused by mutations in the PAH gene itself, and the RFLPs could be used effectively for prenatal diagnosis and carrier detection of PKU in affected families. Use of the PKU haplotypes based on these eight RFLPs would establish disease status in approximately 87% of siblings at risk, although three RFLPs alone (detected with the restriction enzymes Pvu II, Xmn I, and EcoR R) are nearly as effective.
AB - Restriction fragment length polymorphisms (RFLPs) detected in the human genome by means of a cDNA clone of phenylalanine hydroxylase (PAH) segregate concordantly with phenylketonuria (PKU) in several families. To establish the usefulness of these DNA polymorphisms for prenatal diagnosis of PKU the genotypes and chromosomal haplotypes of eight RFLPs at the PAH locus were determined in 46 families, each with one or more affected children. 34 of these families were informative for linkage analysis, giving a maximum probability of 109:1 in favour of tight linkage between PKU and the PAH RFLP haplotypes. Thus the deficiency of hepatic PAH in PKU patients is caused by mutations in the PAH gene itself, and the RFLPs could be used effectively for prenatal diagnosis and carrier detection of PKU in affected families. Use of the PKU haplotypes based on these eight RFLPs would establish disease status in approximately 87% of siblings at risk, although three RFLPs alone (detected with the restriction enzymes Pvu II, Xmn I, and EcoR R) are nearly as effective.
UR - http://www.scopus.com/inward/record.url?scp=0022599597&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(86)90771-3
DO - 10.1016/S0140-6736(86)90771-3
M3 - Article
C2 - 2868252
AN - SCOPUS:0022599597
SN - 0140-6736
VL - 327
SP - 229
EP - 232
JO - The Lancet
JF - The Lancet
IS - 8475
ER -