Evidence for male X chromosomal mosaicism in X-linked agammaglobulinemia.
X-Linked agammaglobulinemia (XLA) is a severe antibody deficiency disease in man, resulting from an arrest in differentiation of pre-B cells. XLA is recessive: female carriers do not exhibit antibody deficiency, but manifest an exclusive inactivation of the XLA-carrying X chromosome in all peripheral blood B lymphocytes. An exclusive inactivation of the paternal X chromosome in the B lymphocytes of all daughters of a male who had no agammaglobulinemia demonstrated that the XLA defect can originate from healthy males. These males are X chromosomal mosaics. X-Chromosomal RFLP segregation analyses in other XLA pedigrees suggest a frequent introduction of XLA by healthy males. This implies that XLA often originates from mitotic errors, either at postmeiotic or early postzygotic stages.
Hendriks
R W
RW
Department of Immunohaematology, University Medical Center, Leiden, The Netherlands.
Mensink
E J
EJ
Kraakman
M E
ME
Thompson
A
A
Schuurman
R K
RK
D000361:Agammaglobulinemia / Q000235:genetics*; D015139:Blotting, Southern; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D009030:Mosaicism; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D014960:X Chromosome