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X‐inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency
Author(s) -
Yorifuji Tohru,
Muroi Junko,
Uematsu Ayumi,
Tanaka Koichi,
Kiwaki Koji,
Endo Fumio,
Matsuda Ichiro,
Nagasaka Hironori,
Furusho Kenshi
Publication year - 1998
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.1998.5440415.x
Subject(s) - ornithine transcarbamylase , hyperammonemia , phenotype , ornithine transcarbamylase deficiency , asymptomatic , medicine , urea cycle , endocrinology , ornithine carbamoyltransferase , asymptomatic carrier , liver disease , biology , ornithine , genetics , gene , amino acid , arginine
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.