Extensive analysis of mosaicism in a case of Turner syndrome - The experience of 287 cytogenetic laboratories

Objective.-To assemble and interpret karyotype data provided as part of the College of American Pathologists/American College of Medical Genetics Cyto genetics Proficiency Testing Program. Data Sources, Extraction, and Synthesis.-The Cytogenetics Resource Committe e requested data on all cells analyzed in a 1994 whole-blood specimen chall enge. In that study, 287 participating laboratories analyzed a total of 142 97 cells derived from a sample drawn from an adult donor with Turner syndro me. This individual had previously been found to have mosaicism, including cell lines with X structural anomalies along with monosomy X, making this a n excellent challenge for a multicenter cytogenetic survey. Results and Conclusions.-Analysis of the data from this extensive study rev ealed mosaicism of up to 10 different sex chromosome complements involving the X chromosome with and without a small ring X or a derivative X chromoso me. In the routine cytogenetic analysis performed by the participating labo ratories, cell lines observed, in decreasing order of prevalence, included 45,X (n = 8357 cells), 46,X,r(X) (n = 3597), 46,X,der(X)t(X;X) (n = 2237), 46,XX (n = 93), 47,X,r(X),r(X) (n = 5), 47,X,der (X)t(X;X),der(X)t(X;X) (n = 3), 47,XX,r(X) (n = 2), and one observation each of 47,XX,der(X)t(X;X), 4 7,X,der(X)t (X;X),r(X), and 47,XXX. Our molecular cytogenetic data,as well as detailed analysis of G-banded chromosomes, suggest the nomenclature for these 2 abnormal X chromosomes as r(X)(p11.3q21.3) and der(X)t(X;X)(p11.3;q 21.3), and we discuss models for the concomitant formation of these 2 entit ies. Both the degree of analysis and the extensive mosaicism that was disco vered in this study are exceptional, and similar reported cases as well as possible mechanisms for the observed X chromosome instability are reviewed.