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Eur J Hum Genet. 2014 Sep;22(9):1077-84. doi: 10.1038/ejhg.2013.295. Epub 2014 Jan 8.

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

Author information

1
1] Department of Clinical Genetics, Erasmus Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands [2] Department of Paediatric Surgery, Erasmus Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.
2
Department of Reproduction and Development, Erasmus Medical Centre, Rotterdam, The Netherlands.
3
Department of Clinical Genetics, Erasmus Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.
4
Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
5
Department of Paediatric Surgery, Erasmus Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.

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.

PMID:
24398799
PMCID:
PMC4135408
DOI:
10.1038/ejhg.2013.295
[Indexed for MEDLINE]
Free PMC Article

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