There is no conflict of interest.
Familial Microdeletion of 17q24.3 Upstream of SOX9 Is Associated With Isolated Pierre Robin Sequence Due to Position Effect
Article first published online: 26 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 5, pages 1167–1172, May 2013
How to Cite
2013. Familial microdeletion of 17q24.3 upstream of SOX9 is associated with isolated Pierre Robin sequence due to position effect. Am J Med Genet Part A 161A:1167–1172., , .
Author contributions: I.A. helped interpreting the microarray results and wrote manuscript draft. K.D. evaluated the patient and provided clinical information. F.Q.-R. made the microarray diagnosis and wrote manuscript draft.
- Issue published online: 22 APR 2013
- Article first published online: 26 MAR 2013
- Manuscript Accepted: 13 DEC 2012
- Manuscript Received: 8 OCT 2012
- Pierre Robin sequence;
- chromosome microarray analysis;
- deletion 17q24.3;
- position effect;
Pierre Robin sequence (PRS) is a malformation pattern characterized by the core triad of retrognathia, glossoptosis, and cleft palate that causes difficulty in glossopharyngeal–laryngeal–vagal functions. The etiology of PRS remains largely unknown; previous reports have suggested that it is caused by intrauterine constriction or external conditions such as oligohydramnios, breech position, or abnormal uterine anatomy. Genetic causes include occurrence as a manifestation of many single gene conditions and chromosomal rearrangements. Positional effect on some loci or genes, including SOX9 has also been posited as a cause. Here, we report on an 18-month-old girl born with isolated PRS. Clinical chromosome microarray analysis (CMA) revealed a maternally inherited ∼623 kb microdeletion that is −725 kb upstream of 5′ SOX9 at chromosome locus 17q24.3. Her mother had cleft palate. This region, although devoid of any genes, is known to have a position effect on SOX9 due to elimination of highly conserved non-coding cis-regulatory elements. This report supports the evidence that deregulation of an intact SOX9 coding region is a cause of or associated with isolated PRS, and provides further evidence that CMA in the clinical setting is a powerful tool in detecting microdeletions in gene “desert” regions that have pathogenic position effect on specific genes. © 2013 Wiley Periodicals, Inc.