TRISOMY-X IN A FEMALE MEMBER OF A FAMILY WITH X-LINKED SEVERE COMBINED IMMUNODEFICIENCY - IMPLICATIONS FOR CARRIER DIAGNOSIS

We describe a family affected by X linked severe combined immunodefici ency (SCIDX1) in which genetic prediction of carrier status was made u sing X chromosome inactivation studies together with limited genetic l inkage analysis. Linkage studies in this family showed a confusing pat tern of inheritance for the X chromosome, A female with a random patte rn of X chromosome inactivation in her T cells appeared to have inheri ted an X chromosome with four recombinations within 10 cM. The odds of this happening in a single meiotic event make this an unlikely explan ation. Data obtained from studying the X chromosomes of her two unaffe cted sons showed that this could be explained simply on the basis of h er having inherited three alleles each of the relevant polymorphic DNA loci. We used fluorescent in situ hybridisation (FISH) to confirm tha t this person had inherited three complete X chromosomes. Thus, althou gh the results from X chromosome inactivation analysis indicated that this subject was not a carrier of the affected chromosome, FISH and ge netic Linkage analysis showed clearly that the affected chromosome had been inherited, The implications of this finding for diagnosis of car rier status in this family and for other families with X linked inheri ted immunodeficiencies is discussed.