Presence of XIST specific sequences and apparent failure of X dosage compensation by inactivation in a patient with a severe Turner phenotype and mosaicism for X chromosome abnormalities

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133648

Bent-Williams, A H; Felton, S M; Driscoll, D J ^[1]

---

1. Univ. of Florida, Gainesville, FL (United States); and others

An XIST FISH analysis and a late replication chromosome study was performed for a 10 year old female with Turner stigmata, mental retardation, multiple congenital anomalies and a cytogenetic mosaicism of 45,X,inv(9)(p11q13)/46,X,del(X)(q22),inv(9)(p11q13)/46,X,+mar,inv(9)(p11q13). The X chromosomes from a cell line in which one was deleted for the distal long arm segment (breakpoint of Xq22), observed in 6% of metaphase cells from peripheral blood and 23.3% of metaphase cells from skin fibroblasts, did not demonstrate an asynchronous or differential staining pattern by BrDU techniques. However, both the normal X chromosome and the deleted X chromosome were demonstrated to contain XIST specific sequences by FISH analysis. A very small marker chromosome, observed in 6% of metaphase cells from peripheral blood and 3.3% of metaphase cells from skin fibroblasts, appeared to consist exclusively of X chromosome alpha satellite centromeric material (DXZ1). This finding was consistent with the morphology of the marker chromosome as observed by conventional G-banding. Due to its small size and low level frequency, analysis by late replication BrDU techniques was not possible. The predominate cell line containing a signal X chromosome was observed in 88% of metaphase cells from peripheral blood and 73.3% of metaphase cells from skin fibroblasts. This case is significant because: (1) it represents another case of an X chromosome abnormality in which XIST is apparently present but not expressed; and (2) the more severe phenotype expressed is probably attributable to the failure of X gene dosage compensation by inactivation.

• OSTI ID: 133648
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BANDING TECHNIQUES
CENTROMERES
CHROMOSOMAL ABERRATIONS
CONGENITAL MALFORMATIONS
DETECTION
DNA HYBRIDIZATION
DNA SEQUENCING
FLUORESCENCE
GENES
HUMAN X CHROMOSOME
KARYOTYPE
MENTAL DISORDERS
MOSAICISM
PATIENTS
PHENOTYPE
STRUCTURE-ACTIVITY RELATIONSHIPS