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A mutation of the p63 gene in non-syndromic cleft lip
  1. P Leoyklang1,
  2. P Siriwan2,
  3. V Shotelersuk1
  1. 1Division of Medical Genetics and Metabolism, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  2. 2Division of Plastic Surgery, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  1. Correspondence to:
 Dr V Shotelersuk
 Head of Division of Medical Genetics and Metabolism, Department of Pediatrics, Sor Kor Building 11th floor, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand; vorasuk.s{at}chula.ac.th

Abstract

Mutations in the p63 gene (TP63) underlie several monogenic malformation syndromes manifesting cleft lip with or without cleft palate (CL/P). We investigated whether p63 mutations also result in non-syndromic CL/P. Specifically, we performed mutation analysis of the 16 exons of the p63 gene for 100 Thai patients with non-syndromic CL/P. In total, 21 variant sites were identified. All were single nucleotide changes, with six in coding regions, including three novel non-synonymous changes: S90L, R313G, and D564H. The R313G was concluded to be pathogenic on the basis of its amino acid change, evolutionary conservation, its occurrence in a functionally important domain, its predicted damaging function, its de novo occurrence, and its absence in 500 control individuals. Our data strongly suggest, for the first time, a causative role of a heterozygous mutation in the p63 gene in non-syndromic CL/P, highlighting the wide phenotypic spectrum of p63 gene mutations.

  • AEC, ankyloblepharon-ectodermal dysplasia-clefting syndrome
  • CL/P, cleft lip with or without cleft palate
  • DB, DNA binding
  • EEC, ectrodactyly-ectodermal dysplasia-clefting syndrome
  • ESE, exonic splicing enhancer
  • RHS, Rapp-Hodgkin syndrome
  • SAM, sterile α-motif, SR, serine/arginine-rich
  • TA, transactivating
  • and TI, transactivation inhibitory
  • non-syndromic cleft lip
  • p63
  • mutations

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Footnotes

  • Competing interests: there are no competing interests

  • We received written consents from the patients’ legal guardians for publication of the images.

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