Structural and numerical changes of chromosome X in patients with esophageal atresia.

Abstract

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is a relatively common birth defect often associated with additional congenital anomalies such as vertebral, anal, cardiovascular, renal and limb defects, the so-called VACTERL association. Yet, little is known about the causal genetic factors. Rare case reports of gastrointestinal anomalies in children with triple X syndrome prompted us to survey the incidence of structural and numerical changes of chromosome X in patients with EA/TEF. All available (n=269) karyotypes of our large (321) EA/TEF patient cohort were evaluated for X-chromosome anomalies. If sufficient DNA material was available, we determined genome-wide copy number profiles with SNP array and identified subtelomeric aberrations on the difficult to profile PAR1 region using telomere-multiplex ligation-dependent probe amplification. In addition, we investigated X-chromosome inactivation (XCI) patterns and mode of inheritance of detected aberrations in selected patients. Three EA/TEF patients had an additional maternally inherited X chromosome. These three female patients had normal random XCI patterns. Two male EA/TEF patients had small inherited duplications of the XY-linked SHOX (Short stature HOmeoboX-containing) locus. Patients were small for gestational age at birth (<P5) and had additional, mostly VACTERL associated, anomalies. Triple X syndrome is rarely described in patients with EA/TEF and no duplications of the SHOX gene were reported so far in these patients. As normal patterns of XCI were seen, overexpression of X-linked genes that escape XCI, such as the SHOX gene, could be pathogenic by disturbing developmental pathways.

• Authors: Erwin Brosens, Elisabeth M de Jong, Tahsin Stefan Barakat, Bert H Eussen, Barbara D'haene, Elfride De Baere, Hannah Verdin, Pino J Poddighe, Robert-Jan Galjaard, Joost Gribnau, Alice S Brooks, Dick Tibboel, Annelies de Klein
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 22 Issue 9 Pg. 1077-84 (Sep 2014) ISSN: 1476-5438 [Electronic] England
• PMID: 24398799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Homeodomain Proteins
• SALL1 protein, human
• SHOX protein, human
• Short Stature Homeobox Protein
• Transcription Factors

Topics

• Adult
• Anal Canal (abnormalities)
• Chromosome Aberrations
• Chromosomes, Human, X (genetics)
• Esophageal Atresia (diagnosis, genetics)
• Esophagus (abnormalities)
• Female
• Genetic Loci
• Heart Defects, Congenital (diagnosis, genetics)
• Homeodomain Proteins (genetics)
• Humans
• Karyotype
• Kidney (abnormalities)
• Limb Deformities, Congenital (diagnosis, genetics)
• Male
• Polymorphism, Single Nucleotide
• Sex Chromosome Aberrations
• Sex Chromosome Disorders of Sex Development (diagnosis, genetics)
• Short Stature Homeobox Protein
• Spine (abnormalities)
• Trachea (abnormalities)
• Transcription Factors (genetics)
• Trisomy (diagnosis, genetics)
• X Chromosome Inactivation