title: Trisomy Xp and partial tetrasomy Xq resulting from gain of a rearranged X chromosome in a female fetus: pathogenic or not?
abstract: Cytogenetic analysis of chorionic villous sampling revealed a mosaic karyotype with gain of a rearranged X chromosome. Microarray and additional studies indicated that the rearranged X carried an inverted duplication, a deletion and a satellited Xqter. Gain of this rearranged X was confirmed by follow-up amniocentesis and postnatal cord blood sample. A full-term infant girl was delivered and showed normal physical findings at both birth and 21-month follow-up examinations. Late replication studies demonstrated that the rearranged X was inactivated in all abnormal cells analyzed. Skewed X-inactivation may suppress the potentially deleterious effects of genomic imbalance; however, gain of X chromosomes, particularly rearranged X chromosomes, often presents challenges for prenatal genetic counseling. The gradation of clinical phenotype severity generally correlates with the number of additional X chromosomes. However, the X chromosome regions responsible for the abnormal phenotypes are poorly understood. This case will further elucidate the phenotypic effects of X inactivation and X chromosome abnormalities.
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco. 185 Berry Street, Suite# 290, Campus Box 0134, San Francisco, CA 94107 USA.
authors.forename: Maria
authors.identifier: 0000-0002-0732-4492
authors.initials: M
authors.lastname: Yiu
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco. 185 Berry Street, Suite# 290, Campus Box 0134, San Francisco, CA 94107 USA.
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Clinical Cytogenetics Laboratory, UCSF Medical Center, San Francisco, CA USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Ki
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco. 185 Berry Street, Suite# 290, Campus Box 0134, San Francisco, CA 94107 USA.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Yu
keywords: Amniocentesis; Array CGH; Chorionic villus sampling; Genetic counseling; High risk pregnancy; Prenatal diagnosis; Sex chromosome abnormality; X inactivation