Taiwanese Journal of Obstetrics and Gynecology
Volume 44, Issue 1 , Pages 52-56, March 2005

Prenatal Diagnosis of Classical Phenylketonuria with Polymerase Chain Reaction, Automatic Sequencing, and Linkage Analysis with Short Tandem Repeats

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan

Received 3 September 2004; received in revised form 20 September 2004; accepted 20 September 2004.

Article Outline

Summary 

Objective

To share our experience of prenatal classical phenylketonuria (PKU) diagnosis using the polymerase chain reaction (PCR), automatic sequencing, and linkage analysis with short tandem repeats (STRs).

Materials and Methods

Eight pregnant women who had delivered one baby with confirmed classical PKU were enrolled. They underwent amniocentesis and blood sampling. Genomic DNA was extracted from peripheral blood leukocytes and amniotic cells. Oligonucleotide primers for each specific exon, intron, enhancer, and STR of intron 3 were used for PCR amplification. The sequence was analyzed and the mutant pattern was determined.

Results

Of the eight fetuses, one was normal, one had disease, five were disease-free carriers, and one test was indeterminate. Identified mutations included R408Q (n = 4), R241C (n = 3), R413P (n = 1), A434D (n = 1), and G257V (n = 1).

Conclusion

The combination of amniocentesis and PCR can successfully detect fetuses with classical PKU early in pregnancy. Based on our experience, common mutations were R408Q and R241C.

Key Words:  hyperphenylalaninemia , phenylalanine hydroxylase , phenylketonuria , polymerase chain reaction , prenatal diagnosis , short tandem repeat

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Scriver CR , Hurtubise M , Konecki D , et al.   PAHab 2003: what a locus-specific knowledgebase can do . Hum Mutat . 2003;21:333–344
  2. Guldberg P , Rey F , Zschocke J , et al.   A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype . Am J Hum Genet . 1998;63:71–79
  3. Guldberg P , Romano V , Ceratto N , et al.   Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: implications for diagnosis of hyperphenylalaninemia in southern Europe . Hum Mol Genet . 1993;2:1703–1707
  4. Chen KJ , Chao HK , Hsiao KJ , Su TS . Identification and characterization of a novel liver-specific enhancer of the human phenylalanine hydroxylase gene . Hum Genet . 2002;110:235–243
  5. Bickel H , Gerrard J , Hickmans EM . Influence of phenylalanine intake on phenylketonuria . Lancet . 1953;ii:812–823
  6. Guthrie R , Susi A . A simple phenylalanine method for detecting phenylketonuria in a large population of newborn infants . Pediatrics . 1963;32:338–343
  7. Zschocke J . Phenylketonuria mutations in Europe . Hum Mutat . 2003;21:345–356
  8. Scriver CR , Kaufman S , Eisensmith RC , Wool SLC . The hyperphenylalaninemias . In:  Scriver CR ,  Beaudet AL ,  Sly WS ,  Valle D editor. The Metabolic and Molecular Basis of Inherited Disease . New York: McGraw Hill; 2001;p. 667–1724
  9. Gable M , Williams M , Stephenson A , et al.   Comparative multiplex dosage analysis detects whole exon deletions at the phenylalanine hydroxylase locus . Hum Mutat . 2003;21:379–386
  10. Tighe O , Dunican D , O'Neill C , et al.   Genetic diversity within the R408W phenylketonuria mutation lineage in Europe . Hum Mutat . 2003;21:387–393
  11. Pronina N , Giannattasio S , Lattanzio P , Lugovska R , Vevere P , Kornejeva A . The molecular basis of phenylketonuria in Latvia . Hum Mutat . 2003;21:398–399
  12. Kasnauskiene J , Giannattasio S , Lattanzio P , Cimbalistiene L , Kucinskas V . The molecular basis of phenylketonuria in Lithuania . Hum Mutat . 2003;21:398
  13. Chien YH , Chiang SC , Huang A , et al.   Mutation spectrum in Taiwanese patients with phenylalanine hydroxylase deficiency and a founder effect for the R241C mutation . Hum Mutat . 2003;21:345–356

PII: S1028-4559(09)60107-8

doi:10.1016/S1028-4559(09)60107-8

Taiwanese Journal of Obstetrics and Gynecology
Volume 44, Issue 1 , Pages 52-56, March 2005

Article Tools