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

Journal Article · Fri Aug 23 04:00:00 EDT 1996 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/(SICI)1096-8628(19960823)64:3<459::AID-AJMG3>3.0.CO;2-K· OSTI ID:539401

Hoshide, Ryuuji; Matsuura, Toshinobu; Endo, Fumio ^[1]

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1. 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, Journal Name: American Journal of Medical Genetics Journal Issue: 3 Vol. 64; ISSN 0148-7299; ISSN AJMGDA
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
CODONS
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
ENZYME ACTIVITY
FETUSES
GENE MUTATIONS
GENETICS
HEREDITARY DISEASES
INTRONS
METABOLIC DISEASES
NUCLEOTIDES
ORNITHINE
PATIENTS
POLYMERASE CHAIN REACTION
RISK ASSESSMENT
SCREENING
SPLICING
STRUCTURE-ACTIVITY RELATIONSHIPS
UREA