Random X inactivation resulting in mosaic nullisomy of region Xp21.1----p21.3 associated with heterozygosity for ornithine transcarbamylase deficiency and for chronic granulomatous disease.
A young woman with normal gonadal development and mild mental retardation was found to have a small de novo interstitial deletion of most of band Xp21, karyotype designation 46,X,del(X) (pter----p21.3:: p21.1----qter). Replication studies on lymphocytes and skin fibroblasts revealed that in 45% of cells the normal X was late replicating. Somatic cell hybrids between her fibroblasts and HPRT-deficient Chinese hamster cells were obtained and selected for and against retention of the active human X chromosome. In several independent hybrids the deleted X was retained in the active state. Partial ornithine transcarbamylase (ornithine carbamoyltransferase EC 2.1.3.3) (OTC) deficiency was documented by elevated urinary orotic acid excretion and increased serum glutamine after a protein load. This confirms the mapping of the structural gene for OTC to this deletion. Testing of neutrophil function revealed heterozygosity for chronic granulomatous disease (CGD) suggesting that a gene for CGD maps within the deletion. Thus, X inactivation mosaicism is also present in hepatocytes and neutrophilic granulocytes. Random X inactivation in a female with an Xp deletion has not been previously reported. The cells from this patient and the somatic cell hybrids containing her deleted X chromosome in the absence of the normal X provide material for the precise mapping of X linked genes and DNA sequences on the short arm of the human X chromosome.
D000328:Adult; D002478:Cells, Cultured; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002873:Chromosome Fragility; D003878:Dermatoglyphics; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D008214:Lymphocytes / Q000166:cytology; D009030:Mosaicism; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D012867:Skin / Q000473:pathology; D014960:X Chromosome