Abstract
BackgroundWe investigated a large family with Pierre Robin sequence (PRS).Aim of the studyThis study aims to determine the genetic cause of PRS.ResultsThe reciprocal translocation t(4;6)(q22;p21) was identified to be segregated with PRS in a three-generation family. Whole-genome sequencing and Sanger sequencing successfully detected breakpoints in the intragenic regions of BMRP1B and GRM4. We hypothesized that PRS in this family was caused by (i) haploinsufficiency for BMPR1B or (ii) a gain of function mechanism mediated by the BMPR1B-GRM4 fusion gene. In an unrelated family, we identified another BMPR1B-splicing mutation that co-segregated with PRS.ConclusionWe detected two BMPR1B mutations in two unrelated PRS families, suggesting that BMPR1B disruption is probably a cause of human PRS.MethodsGTG banding, comparative genomic hybridization, whole-genome sequencing, and Sanger sequencing were performed to identify the gene causing PRS.
Highlights
Pierre Robin sequence (PRS, MIM: 261800), known as Pierre Robin syndrome, is a condition characterized by micrognathia, cleft palate, and glossoptosis [1,2,3]
No pathogenic copy number variations (CNVs) were detected near 4q22, 6p21, or any other location in the PRS-affected family 01
Comparative genomic hybridization (CGH) was performed on the proband (II:1) in family 02
Summary
Pierre Robin sequence (PRS, MIM: 261800), known as Pierre Robin syndrome, is a condition characterized by micrognathia, cleft palate, and glossoptosis (leading to airway obstruction and eventually develops into chonechondrosternon) [1,2,3]. Many studies have identified translocation breakpoints and mutations in the conserved and non-coding elements of SOX9 in patients with PRS; results illustrated that SOX9 disruptions are involved in PRS [7, 8]. Results: The reciprocal translocation t(4;6)(q22;p21) was identified to be segregated with PRS in a three-generation family. We hypothesized that PRS in this family was caused by (i) haploinsufficiency for BMPR1B or (ii) a gain of function mechanism mediated by the BMPR1B-GRM4 fusion gene. We identified another BMPR1Bsplicing mutation that co-segregated with PRS. Conclusion: We detected two BMPR1B mutations in two unrelated PRS families, suggesting that BMPR1B disruption is probably a cause of human PRS. Methods: GTG banding, comparative genomic hybridization, whole-genome sequencing, and Sanger sequencing were performed to identify the gene causing PRS
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