Prenatal monitoring in a family at high risk for ornithine transcarbamylase (OTC) deficiency: A new mutation of an A-to-C transversion in position +4 of intron 1 of the OTC gene that is likely to abolish enzyme activity
- Kumamoto Univ. School of Medicine (Japan); and others
DNA analysis of a male propositus with ornithine transcarbamylase (OTC) deficiency documented an A-to-C substitution in position +4 of intron 1. No other abnormalities were observed in the OTC gene, or at 563 bp upstream of the 5{prime} site, which included a promoter region, or at 383 bp downstream of the termination codon, which included a polyadenylation signal sequence. This mutation produces an RsaI site in the sequence, which was used for prenatal monitoring in the fourth and fifth pregnancies. DNA from amniotic cells in the former case were positive for RsaI digestion and the SRY gene (sex determinant region Y), indicating hemizygosity for the mutant allele. OTC activity was not measureable, and mRNA of the OTC gene was not detected by Northern blotting in the affected fetal liver. RT-PCR (reverse transcription-PCR) demonstrated only the wild-type allele. Thus, the mutation interferes with RNA processing, and an extremely low amount of normally spliced mRNA for the OTC gene seems to have caused the disease in our patient. The fetus of the fifth pregnancy was a normal male, as confirmed postnatally. 25 refs., 5 figs.
- OSTI ID:
- 539401
- Journal Information:
- American Journal of Medical Genetics, Vol. 64, Issue 3; Other Information: PBD: 23 Aug 1996
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
METABOLIC DISEASES
GENETICS
RISK ASSESSMENT
FETUSES
SCREENING
PATIENTS
HEREDITARY DISEASES
ORNITHINE
ENZYME ACTIVITY
GENE MUTATIONS
DNA-CLONING
DNA SEQUENCING
SPLICING
STRUCTURE-ACTIVITY RELATIONSHIPS
NUCLEOTIDES
INTRONS
AMINO ACIDS
CODONS
POLYMERASE CHAIN REACTION
UREA
DNA HYBRIDIZATION