A point mutation and a RNA processing mutation in a carbamyl phosphate synthetase I (CPSI) deficient patient
- Vanderbilt Univ. Medical Center, Nashville, TN (United States)
Deficiency of carbamyl phosphate synthetase I (CPSID) results in a life-threatening disease due to hyperammonemia. A better understanding of the molecular basis of CPSID was achieved by studying the genetic defects in a CPSID patient. CPSI message was analyzed from hepatic tissue through Northern blot analysis, reverse transcription of liver mRNA followed by polymerase chain reaction amplification (RT-PCR), dideoxy fingerprinting, and direct DNA sequencing. Northern blot analysis of the patient revealed a diminished amount of normal sized CPSI message and multiple other bands not detected in controls. Analysis of the amplified coding region revealed a single point mutation leading to an asparagine to lysine substitution at codon 715. The patient`s cDNA was homozygous and genomic DNA heterozygous for the point mutation which was not found in ten unrelated CPSID patients. The point mutation causes a change from a highly-conserved neutral amino acid to a polar basic residue within a nucleotide/bicarbonate binding domain which points to its importance in normal CPSI function. The other allele which was absent in RT-PCR fragements presumably leads to the multi-form poly-A message detected by Northern blot analysis and allows the point mutation to become the dominant expressed allele. These mutations represent the second reported molecular defect in CPSI and the first to involve a mutation in a functional domain and in RNA processing.
- OSTI ID:
- 134220
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0956
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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