title: X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency.
abstract: Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It is X-linked and hemizygous new-born males usually suffer fatal hyperammonemia. In contrast, carrier females manifest variable phenotypes, ranging from asymptomatic carriers to those with severe hyperammonemia. In order to understand the correlation between X-inactivation status and the clinical phenotype of carrier females with this disorder, we analyzed the X-inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and two daughters with severe manifestation. In addition, we obtained tissue samples from various parts of the liver of one of these daughters and analyzed X-inactivation patterns and the residual OTC activities. The X-inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype. However, the X-inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. Interestingly, the degree of X-inactivation varied considerably, even within the same liver.
authors.affiliation: Department of Pediatrics and Transplantation, Kyoto University Hospital, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yorifuji
authors.forename: J
authors.initials: J
authors.lastname: Muroi
authors.forename: A
authors.initials: A
authors.lastname: Uematsu
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Kiwaki
authors.forename: F
authors.initials: F
authors.lastname: Endo
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
authors.forename: H
authors.initials: H
authors.lastname: Nagasaka
authors.forename: K
authors.initials: K
authors.lastname: Furusho
mesh_terms: D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis / Q000235:genetics; D004303:Dosage Compensation, Genetic; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007223:Infant; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010375:Pedigree; D000644:Quaternary Ammonium Compounds / Q000097:blood; D014960:X Chromosome / Q000201:enzymology / Q000235:genetics*
chemical_list: D000644:Quaternary Ammonium Compounds; D004247:DNA; D009954:Ornithine Carbamoyltransferase