Spread of X inactivation on chromosome 15 is associated with a more severe phenotype in a girl with an unbalanced t(X; 15) translocation. Issue 10 (16th July 2014)

• Record Type: Journal Article
• Authors: Yeung, KS; Chee, YY; Luk, HM; Kan, Anita SY; Tang, Mary HY; Lau, Elizabeth T; Shuen, Andrew Y; Lo, Ivan FM; Chan, Kelvin YK; Chung, Brian HY
• Is Part Of: American journal of medical genetics. Volume 164:Issue 10(2014.)
• Page Start: 2521
• Page End: 2528
• Publication Date: 2014-07-16
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36670
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36670-sec-0001" sec-type="section"> <p>We report on a baby girl with multiple congenital abnormalities, including cleft palate, intrauterine growth restriction, and double outlet right ventricle (DORV) with ventricular septal defect. She had an unbalanced chromosome translocation t (X;15) resulting in monosomy 15pter → p10 and trisomy Xq13.1 → q28. All three copies of Xq encompass the <italic>XIST</italic> gene. It is known that X chromosome inactivation could spread to the autosome part of an unbalanced translocation involving chromosome X and an autosome. To confirm the spread of X chromosome inactivation on chromosome 15, we evaluate the methylation change by the HumanMethylation450 BeadChip, a whole genome DNA methylation micorarray that includes 15, 259 probes spanning 717 genes on chromosome 15. Results showed there was gain in DNA methylation of more than 20% in 586 CpG sites spanning the long arm of chromosome 15. We further examined the hypermethylated CpG sites located in CpG‐island promoter, because genes subjected to X chromosome inactivation will have an increase in DNA methylation level in this region. A total of 75 sites representing 24 genes were hypermethylated. Nearly all of these probes are located in region proximal to the breakpoint, from 15q11.2 to 15q21.3 (35Mb) suggesting that X inactivation was spread to the proximal region of 15q. Gain of DNA methylation, especially in the CpG‐island promoter, can result in functional inactivation of genes, and therefore could potentially worsen the phenotype of our patient. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>