Identification of the susceptibility genes for nonsyndromic cleft lip and /or palate

1)非综合征性唇腭裂（CLP）易感基因的鉴定获得了九州大学研究生院齿科学研究科和鹿儿岛大学研究生院医学齿科学研究科伦理委员会的批准。此外，在马来西亚的Harapan Kita儿童和妇产医院的伦理委员会中获得了合作鉴定CLP易感基因的批准。2）在知情同意后，使用伦理委员会批准的方案，在113个三人组中校正了患者和父母的血液样本。对6个非综合征型CLP患者的多发家系进行指甲标本的校正。3）采集血液标本，提取DNA。采用直接测序法和焦磷酸测序法对GABAA受体基因和Fox 2基因的各标记进行基因分型。使用计算程序继续评估每个标记物与非综合征型CLP之间的关联。4）对Ellis-van Creveld综合征的家族性病例，采用直接测序法对MSX 1、EVC和EVC 2基因的每个标记进行基因分型。EVC基因22个外显子中的6个外显子均未检测到突变，有待进一步研究。5）对443例唇腭裂合并面裂患者的唇腭裂合并畸形进行分析。并发畸形发生率以面裂最高（70%），其次为粘膜下腭裂（54.3%）和腭裂（47.4%）。发现它们比CLA（15.3%）和CLP（18.4%）更常见。

1) Approval o identification of the susceptibility genes for nonsyndromic cleft lip and/or palate (CLP) was obtained in the ethics committees in Graduate School of Dental Science in Kyushu University and Graduate School of Medical and dental Sciences in Kagoshima University. Also approval of collaboration for identification of the susceptibility genes for CLP was obtained in the ethics committee in Harapan Kita Children and Maternity Hospital in Indonesia.2) Correcting the blood samples from patient and parents was made in 113 trios after informed consent using protocol approved by the ethic committee. After selection of the multiples families with nonsyndromic CLP patients, the nail samples were corrected from 6 multiples families.3) DNA extraction was made from the blood samples. Genotyping of each marker of the GABAA receptor gene and Fox2 gene was carried out by the direct sequencing and the pyro-sequencing method. Evaluation the associations between each marker and nonsyndromic CLP was continued by using the computational program. Furthermore, selecting the genomic markers on the susceptibility chromosomal regions supposed from latest was made on the samples extracted from multiples families in Harapan Kita Hospital.4) On the familial cases of Ellis-van Creveld syndrome, genotyping of each marker of MSX1, EVC, and EVC2 genes was carried out by the direct sequencing method. No mutation of EVC gene has been detected in the 6 Exons of all 22 Exons, and further studies will be continued.5) Complicated malformation of cleft lip and palate was analyzed on 443 patients with CLP and facial cleft. Incidence complicated malformation was highest in facial cleft (70%), followed by submucous cleft palate (54.3%) and cleft palate (47.4%). They were found to be more frequent than CLA (15.3%) and CLP (18.4%).