Small marker X chromosomes lack the X inactivation center : implications for karyotype/phenotype correlations

• Published in: American journal of human genetics Vol. 55; no. 1; pp. 87 - 95
• Main Authors: WOLFF, D. J, BROWN, C. J, SCHWARTZ, S, DUNCAN, A. M. V, SURTI, U, WILLARD, H. F
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.07.1994
• Subjects: 550900 > Pathology; Adult; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; Centromere - ultrastructure; Child; Child, Preschool; Chromosome aberrations; Chromosome Aberrations - genetics; Chromosome Disorders; Chromosome Mapping; CHROMOSOMES; DISEASES; DNA HYBRIDIZATION; Dosage Compensation, Genetic; ETIOLOGY; Female; GENE AMPLIFICATION; Gene Deletion; Genetic Markers; HEREDITARY DISEASES; HETEROCHROMOSOMES; HUMAN CHROMOSOMES; HUMAN X CHROMOSOME; Humans; HYBRIDIZATION; In Situ Hybridization, Fluorescence; Intellectual Disability - genetics; Karyotyping; Male; Medical genetics; Medical sciences; MENTAL DISORDERS; Mosaicism; Phenotype; Ring Chromosomes; RNA, Long Noncoding; RNA, Untranslated; Telomere; Transcription Factors - biosynthesis; Transcription Factors - genetics; X Chromosome - ultrastructure; X CHROMOSOME 550400 > Genetics; Chromosomal aberration; Breakpoint; Chromosome break; Phenotype; Abnormal X chromosome; Cytogenetics; Abnormal chromosome; Exploration; Molecular biology; Inactivation; Karyotype
• ISSN: 0002-9297; 1537-6605

The abnormal phenotype and/or mental retardation seen in persons with small marker X (mar(X)) chromosomes has been hypothesized to be due to the loss of the X inactivation center (XIC) at Xq13.2, resulting in two active copies of genes in the pericentromeric region. In order to define precisely the DNA content of mar(X) chromosomes and to correlate phenotype with karyotype, we studied small mar(X) chromosomes, using FISH with probes in the juxtacentromeric region. One of the probes was a 40-kb genomic cosmid for the XIST gene, which maps to the smallest interval known to contain the XIC and is thought to be involved in X inactivation. Our findings reveal that small mar(X) chromosomes do not include the XIC and therefore cannot be subject to X inactivation, supporting the premise that abnormal dosage of expressed genes in the pericentromeric region of the X generates the aberrant phenotype seen in patients with small mar(X) chromosomes.