Prenatal genetic diagnosis for phenylketonuria families by combination of linkage analysis and mutation screening

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Author:
HU Hao(Medical Genetic Laboratory of Maternal and Children Health Hospital of Hunan,Changsha 410008,China)
WANG Hua(Medical Genetic Laboratory of Maternal and Children Health Hospital of Hunan,Changsha 410008,China)
TANG Hua(Medical Genetic Laboratory of Maternal and Children Health Hospital of Hunan,Changsha 410008,China)
HU Rong(Medical Genetic Laboratory of Maternal and Children Health Hospital of Hunan,Changsha 410008,China)
ZHOU Ying(Medical Genetic Laboratory of Maternal and Children Health Hospital of Hunan,Changsha 410008,China)
XIE Qiong(Medical Genetic Laboratory of Maternal and Children Health Hospital of Hunan,Changsha 410008,China)
MA Li(Medical Genetic Laboratory of Maternal and Children Health Hospital of Hunan,Changsha 410008,China)
Journal Title:
CHINESE JOURNAL OF PERINATAL MEDICINE
Issue:
Volume 14, Issue 02, 2011
DOI:
10.3760/cma.j.issn.1007-9408.2011.02.003
Key Word:
Phenylketonurias;Phenylalanine hydroxylase;Tandem repeat sequences;Polymorphism,single nucleotide;Linkage (genetics);Mutation;Prenatal diagnosis

Abstract: Objective To explore the prenatal genetic diagnosis for classic phenylketonuria (PKU) families.Methods Probands and their family members from three classic PKU families were analyzed by combining linkage analysis through short tandem repeats (STR) polymorphism and PCR-sequencing for the exons within mutation hot spot of phenylalanine hydroxylase gene.Results Linkage analysis found uninformative for Family 1,while 100 % confirmative information was obtained from Family 2 and 3.Sequencing showed compound heterozygous mutations of phenylalanine hydroxylase gene for all of the three probands.Five mutations were detected,namely Y166X,R243Q,R413P,EX6-96A > G and IVS11-1G> C,and IVS11-1G > C was a novel identified muntation.Information from linkage analysis and mutation screening showed clearly that the fetus of Family 1 and 2 were affected,while normal for Family 3.Conclusions For those PKU families,reliable service of prenatal genetic diagnosis could be provided by combining linkage analysis with mutation screening of phenylalanine hydroxylase gene.

  • [1]顾学范,王治国.中国580万新生儿苯丙酮尿症和先天性甲状腺功能低下症的筛查.中华预防医学杂志,2004,38:99-102.
  • [2]Woo SL,Lidsky AS,Guttler F,et al.Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria.Nature,1983,306:151-155.
  • [3]Goltsov AA,Eisensmith RC,Naughton ER,et al.A single polymorphic STR system in the human phenylalanine hydroxylase gene permits rapid prenatal diagnosis and carrier screening for phenylketonuria.Hum Mol Genet,1993,2:577-581.
  • [4]Song F,Qu YJ,Zhang T,et al.Phenylketonuria mutations in Northern China.Mol Genet Metab,2005,86(Suppl 1):S107-S118.
  • [5]Guldberg P,Romano V,Ceratto N,et al.Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily:implications for diagnosis of hyperphenyl-alaninemia in southern Europe.Hum Mol Genet,1993,2:1703-1707.
  • [6]黄尚志,李辉,苗世英,等.苯丙氨酸羟化酶基因中A/C多态性分析.遗传学报,1996,23:169-173.
  • [7]Zschocke J,Hoffmann GF.Phenylketonuria mutations in Germany.Hum Genet,1999,104:390-398.
  • [8]Wang T,Okano Y,Eisensmith RC,et al.Missense mutations prevalent in Orientals with phenylketonuria:molecular characterization and clinical implications.Genomics,1991,10:449-456.
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