Genetic analysis of the first 4 patients with beta-ureidopropionase deficiency.
beta-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway and it catalyses the irreversible hydrolysis of N-carbamyl-ss-aminoisobutyric acid or N-carbamyl-ss-alanine to beta-aminoisobutyric acid or ss-alanine, ammonia, and CO2. Analysis of the beta-ureidopropionase gene (UPB1) of the first 4 patients presenting with a complete enzyme deficiency, revealed the presence of 2 splice-site mutations (IVS1-2A>G and IVS8-1G>A) and one missense mutation (A85E). RT-PCR analysis of the complete beta-ureidopropionase cDNA suggested that both splice-site mutations lead to a variety of alternative splice variants, with deletions of a single or several exons. The alanine at position 85 was not conserved in other eukaryotic beta-ureidopropionase protein sequences.
van Kuilenburg
A B P
AB
Department of Clinical Chemistry, Academic Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands. a.b.vanKuilenburg@amc.uva.nl
Meinsma
R
R
Assman
B
B
Hoffman
G F
GF
Voit
T
T
Ribes
A
A
Lorente
I
I
Busch
R
R
Mayatepek
E
E
Abeling
N G G M
NG
Wevers
R A
RA
Rutsch
F
F
van Gennip
A H
AH
D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*
D017931:DNA Primers; D018076:DNA, Complementary; D000581:Amidohydrolases; C021590:beta-ureidopropionase