TY - JOUR
T1 - Molecular determination of X inactivation pattern correlates with phenotype in women with a structurally abnormal X chromosome
AU - Wolff, D. J.
AU - Schwartz, S.
AU - Carrel, L.
PY - 2000
Y1 - 2000
N2 - Purpose: To correlate the X inactivation pattern, as determined by one or more molecular assays, with phenotype in individuals with structurally abnormal X chromosomes. Methods: We utilized methylation analysis of androgen receptor (AR) and Fragile X (FMR1) genes and expression studies of an XIST polymorphism to assess X inactivation patterns of 28 females with structurally abnormal X chromosomes. Individuals were placed in one of three categories: (1) completely nonrandom inactivation of one X chromosome, (2) preferential or skewed inactivation of one X chromosome, or (3) random inactivation of either X chromosome. Results: In 19 of 21 cases with complete (>97%) skewing of X inactivation, the phenotype was either normal, consistent with a single gene disorder, or consistent with classical Turner syndrome; two cases with completely nonrandom X inactivation had unexplained mental retardation phenotypes. In contrast, six of seven cases that did not exhibit completely nonrandom X inactivation were phenotypically abnormal. Carriers of two balanced translocations, two duplicated Xs, one deleted X, and one 45,X/46,X,r(X) presented with mental retardation and/or multiple congenital anomalies. Conclusion: In patients with random or skewed X inactivation, the abnormal phenotype was hypothesized to be due to functional nullisomy or disomy of X-linked genes. Based on these results, we propose that X inactivation studies should be performed on all women with structurally abnormal X chromosomes. This should aid in the understanding of abnormal phenotypes in liveborn individuals with abnormal X chromosomes and may help to predict phenotypes for prenatally detected cases in the future.
AB - Purpose: To correlate the X inactivation pattern, as determined by one or more molecular assays, with phenotype in individuals with structurally abnormal X chromosomes. Methods: We utilized methylation analysis of androgen receptor (AR) and Fragile X (FMR1) genes and expression studies of an XIST polymorphism to assess X inactivation patterns of 28 females with structurally abnormal X chromosomes. Individuals were placed in one of three categories: (1) completely nonrandom inactivation of one X chromosome, (2) preferential or skewed inactivation of one X chromosome, or (3) random inactivation of either X chromosome. Results: In 19 of 21 cases with complete (>97%) skewing of X inactivation, the phenotype was either normal, consistent with a single gene disorder, or consistent with classical Turner syndrome; two cases with completely nonrandom X inactivation had unexplained mental retardation phenotypes. In contrast, six of seven cases that did not exhibit completely nonrandom X inactivation were phenotypically abnormal. Carriers of two balanced translocations, two duplicated Xs, one deleted X, and one 45,X/46,X,r(X) presented with mental retardation and/or multiple congenital anomalies. Conclusion: In patients with random or skewed X inactivation, the abnormal phenotype was hypothesized to be due to functional nullisomy or disomy of X-linked genes. Based on these results, we propose that X inactivation studies should be performed on all women with structurally abnormal X chromosomes. This should aid in the understanding of abnormal phenotypes in liveborn individuals with abnormal X chromosomes and may help to predict phenotypes for prenatally detected cases in the future.
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U2 - 10.1097/00125817-200003000-00004
DO - 10.1097/00125817-200003000-00004
M3 - Article
C2 - 11397327
AN - SCOPUS:0034528936
SN - 1098-3600
VL - 2
SP - 136
EP - 141
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 2
ER -