RT Journal Article
SR Electronic
T1 X chromosome inactivation and the diagnosis of X linked disease in females.
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 177
OP 184
DO 10.1136/jmg.30.3.177
VO 30
IS 3
A1 R M Brown
A1 G K Brown
YR 1993
UL http://jmg.bmj.com/content/30/3/177.abstract
AB In studies of female patients with suspected deficiency of the E1 alpha subunit of the pyruvate dehydrogenase complex, we have found that X inactivation ratios of 80:20 or greater occur at sufficient frequency in cultured fibroblasts to make exclusion of the diagnosis impossible in about 25% of cases. Pyruvate dehydrogenase E1 alpha subunit deficiency is an X linked inborn error of metabolism which is well defined biochemically and is unusual in that most heterozygous females manifest the condition. The diagnosis is usually established by measurement of enzyme activity and the level of immunoreactive protein and these analyses are most commonly performed on cultured fibroblasts from the patients. Skewed patterns of X chromosome inactivation make it impossible to exclude the diagnosis if the normal X chromosome is expressed in the majority of cells. While most of the observed variation appears to be the expected consequence of random X inactivation, it may be further exaggerated by sampling and subsequent expansion of the cells for analysis.