1. ¹Division of Medical Genetics and Metabolism, Department of Pediatrics, Chulalongkorn University, Bangkok 10330, Thailand
2. ²Division of Plastic Surgery, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
3. ³Division of Medical Genetics and Metabolism, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Sor Kor Building 11th floor, Bangkok 10330, Thailand

Correspondence: Vorasuk Shotelersuk, Division of Medical Genetics and Metabolism, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Sor Kor Building 11th floor, Bangkok 10330, Thailand. E-mail: vorasuk.s@chula.ac.th

Received 17 January 2006; Accepted 26 April 2006; Published online 26 July 2006.

Abstract

Previous studies observed that MSX1 mutations could contribute to nonsyndromic cleft lip with or without cleft palate (CL/P) in some populations. Of the proposed pathogenic mutations, the P147Q variant was predominant in Vietnamese and present in Filipino populations. We investigated whether MSX1 mutations also contribute to nonsyndromic CL/P in the Thai population. Specifically, we performed mutation analysis covering all the coding regions of the MSX1 gene for 100 Thai patients with nonsyndromic CL/P. A total of eight variant sites were identified. Six were in coding regions, including four nonsynonymous changes, 101C>G (A34G), 440C>A (P147Q), 799G>T (G267C), and 832C>T (P278S). The G267C and P278S variants were predicted to be "probably damaging" by PolyPhen, changed themselves as potential exonic splicing enhancers for serine/arginine-rich proteins, and were not present in 162 control individuals of Thai ethnic background. Unlike all of the previously reported potential missense mutations in MSX1, these two novel potential mutations were found in exon 2 on the C-terminal side of the homeodomain protein. Moreover, in contrast to previous reports, we found the P147Q variant in 8 out of 100 Thai controls and an association between the variant and CL/P in our population could not be detected, suggesting that it is not pathogenic. Our data support that MSX1 mutations are found in 2% of cases of CL/P and should be considered for genetic counseling implications, but suggest that the P147Q variant is not pathogenic.