Partial duplication and point mutations of the ornithine carbamoyl transferase (OCT) gene in congenital hyperammonaemia
- Hopital des Enfants-Malades, Paris (France)
ACT deficiency is an enzymopathy of the urea cycle inherited as a partially dominant X-linked trait. Affected males often die during the neonatal period with untractable hyperammonaemic coma but may sometimes present with a late onset disease. Heterozygous females are sometimes symptomatic. Twenty-two unrelated patients (18 males and 4 females) were studied by single strand conformational polymorphism (SSCP) analysis followed by direct sequencing of the OCT exons. Nine of them were found to carry point mutations already reported by others (G50Z, E87K, L88N, R827, R141Z, P225L) or by our group (R277W, 2 patients). A duplication (4 bp) in exon 5 (nt177-XTCACTCAC Xnt178) was found in a male patient with a severe neonatal OCT deficiency. This change led to a frameshift mutation with no in-frame stop codon. To our knowledge, this is the first duplication reported in OCT deficiency. Eight novel missense mutations were found in 12 additional patients: R40H (exon 2, 3 patients), C109S (exon 4, 1 patient), T125M (exon 5, 1 patient), R129Q (exon 5, 3 patients), G188R (exon 6, 1 patient), A209V (exon 6, 1 patient), H302L (exon 9, 2 patients). Four of these mutations occurred in CpG doublets and all of them involved conserved regions of the gene. No such alterations were found in 70 control genes. Phenotype-genotype correlations will be discussed.
- OSTI ID:
- 134210
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0946
- 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
Similar Records
Mutations in the X-linked E{sub 1}{alpha} subunit of pyruvate dehydrogenase: Exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex
X-linked Alport syndrome: An SSCP-based mutation survey over all 51 exons of the COL4A5 gene