title: Familial microdeletion of 17q24.3 upstream of SOX9 is associated with isolated Pierre Robin sequence due to position effect.
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 ~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.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA.
authors.forename: Ina E
authors.initials: IE
authors.lastname: Amarillo
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Dipple
authors.forename: Fabiola
authors.initials: F
authors.lastname: Quintero-Rivera
mesh_terms: D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D005351:Fibromatosis, Gingival / Q000235:genetics*; D006801:Humans; D006983:Hypertrichosis / Q000235:genetics*; D007223:Infant; D020411:Oligonucleotide Array Sequence Analysis; D010855:Pierre Robin Syndrome / Q000235:genetics*; D055758:SOX9 Transcription Factor / Q000235:genetics*
chemical_list: D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human