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  • Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement

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Chromosomal rearrangements
Short report
Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement
  1. Juwon Kim1,
  2. Hong-Hee Won2,3,4,
  3. Yoonjung Kim1,
  4. Jong Rak Choi5,
  5. Nae Yu5,
  6. Kyung-A Lee5
  1. 1Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
  2. 2Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
  3. 3Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
  4. 4Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
  5. 5Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
  1. Correspondence to Dr Kyung-A Lee, Department of Laboratory Medicine, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 135-720, Korea; kal1119{at}yuhs.ac

Abstract

Background Craniosynostosis (CRS) is a premature closure of calvarial sutures caused by gene mutation or environmental factors or interaction between the two. Only a small proportion of non-syndromic CRS (NSC) patients have a known genetic cause, and thus, it would be meaningful to search for a causative gene disruption for the development NSC. We applied a whole genome sequencing approach on a 15-month-old boy with sagittal and metopic synostosis to identify a gene responsible for the development of the disease.

Methods and results Conventional chromosome study revealed a complex paracentric inversion involving 2q14.3 and 2q34. Array comparative genomic hybridisation did not show any copy number variation. Multicolour banding analysis was carried out and the breakpoints were refined to 2q14 and 2q34. An intronic break of the PTH2R gene was detected by whole genome sequencing and fluorescence in situ hybridisation analysis confirmed disruption of PTH2R.

Conclusions We report PTH2R as a gene that is disrupted in NSC. The disruption of the PTH2R gene may cause uncontrolled proliferation and differentiation of chondrocytes, which in turn results in premature closure of sutures. This addition of PTH2R to the list of genes associated with NSC expands our understanding of the development of NSC.

  • Chromosomal
  • Clinical genetics
  • Developmental

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/jmedgenet-2015-103001

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