PMID- 10220141
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20131121
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 13
IP  - 4
DP  - 1999
TI  - Dominant negative allele (N47D) in a compound heterozygote for a variant of
      6-pyruvoyltetrahydropterin synthase deficiency causing transient
      hyperphenylalaninemia.
PG  - 286-9
AB  - Mutations in the 6-pyruvoyltetrahydropterin synthase (PTPS) gene result in
      persistent hyperphenylalaninemia and severe catecholamine and serotonin
      deficiencies. We investigated at the DNA level a family with a PTPS-deficient
      child presenting with an unusual form of transient hyperphenylalaninemia. The
      patient exhibited compound heterozygosity for the PTPS-mutant alleles N47D and
      D116G. Transfection studies with single PTPS alleles in COS-1 cells showed that
      the N47D allele was inactive, while D116G had around 66% of the wild-type
      activity. Upon co-transfection of two PTPS alleles into COS-1 cells, the N47D
      allele had a dominant negative effect on both the wild-type PTPS and the D116G
      mutant with relative reduction to about 20% of control values. Whereas the mother
      and the father had reduced enzyme activity in red blood cells (34.7% and 51.7%,
      respectively) and skin fibroblasts (2.8% and 15.4%, respectively), the clinically
      normal patient had in these cells activities at the detection limits, although
      PTPS-cross-reactive material was present in the fibroblasts. The specifically low
      PTPS activity in the mother's cells corroborated the evidence of a dominant
      negative effect of the maternal N47D allele on wild-type PTPS.
FAU - Scherer-Oppliger, T
AU  - Scherer-Oppliger T
AD  - Division of Clinical Chemistry and Biochemistry, University Children's Hospital, 
      Zurich, Switzerland.
FAU - Matasovic, A
AU  - Matasovic A
FAU - Laufs, S
AU  - Laufs S
FAU - Levy, H L
AU  - Levy HL
FAU - Quackenbush, E J
AU  - Quackenbush EJ
FAU - Blau, N
AU  - Blau N
FAU - Thony, B
AU  - Thony B
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 47E5O17Y3R (Phenylalanine)
RN  - EC 4.6.- (Phosphorus-Oxygen Lyases)
RN  - EC 4.6.10 (6-pyruvoyltetrahydropterin synthase)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Female
MH  - *Genes, Dominant
MH  - *Heterozygote
MH  - Humans
MH  - Male
MH  - Phenylalanine/*blood
MH  - Phosphorus-Oxygen Lyases/blood/*deficiency
MH  - Polymerase Chain Reaction
MH  - Transfection
EDAT- 1999/04/29 02:03
MHDA- 2000/06/22 10:00
CRDT- 1999/04/29 02:03
PHST- 1999/04/29 02:03 [pubmed]
PHST- 2000/06/22 10:00 [medline]
PHST- 1999/04/29 02:03 [entrez]
AID - 10.1002/(SICI)1098-1004(1999)13:4<286::AID-HUMU4>3.0.CO;2-C [pii]
AID - 10.1002/(SICI)1098-1004(1999)13:4<286::AID-HUMU4>3.0.CO;2-C [doi]
PST - ppublish
SO  - Hum Mutat. 1999;13(4):286-9. doi:
      10.1002/(SICI)1098-1004(1999)13:4<286::AID-HUMU4>3.0.CO;2-C.