Familial Microdeletion of 17q24.3 Upstream of SOX9 Is Associated With Isolated Pierre Robin Sequence Due to Position Effect

Ina E. Amarillo, Katrina M. Dipple, Fabiola Quintero-Rivera

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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 ∼623kb microdeletion that is -725kb 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.

Original languageEnglish
Pages (from-to)1167-1172
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • Chromosome microarray analysis
  • Deletion 17q24.3
  • Pierre Robin sequence
  • Position effect
  • SOX9

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