Skewed X-inactivation in carriers of X-linked dyskeratosis congenita.
A gene causing Dyskeratosis Congenita (DC), a rare genetic disorder associated with bone marrow failure, has been mapped to chromosome Xq28, but autosomal inheritance of the disease has also been reported. We have investigated the pattern of X-inactivation in the peripheral blood of carriers of DC using the methylation-sensitive Hpa II site in the androgen receptor gene (HUMARA). In 5 different families in which the inheritance of DC appears to be X-linked, all 16 carriers showed skewed X-inactivation patterns. These cases indicate that, in the hematopoiesis of heterozygous females, cells expressing the normal DC allele have a growth advantage over cells that express the mutant allele. In 7 other families with sporadic cases of DC or with an uncertain pattern of inheritance, both skewed and normal patterns of X-inactivation were observed. In these families or where crucial family members are unavailable, the study of X-inactivation patterns will add to linkage analysis in providing information about carrier status.
Vulliamy
T J
TJ
Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Knight
S W
SW
Dokal
I
I
Mason
P J
PJ
D002874:Chromosome Mapping; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007971:Leukoplakia / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009260:Nail Diseases / Q000235:genetics*; D010375:Pedigree; D010859:Pigmentation Disorders / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D012729:Sex Chromosome Aberrations / Q000235:genetics; D013577:Syndrome
D011944:Receptors, Androgen