Rungnapa Ittiwut1,2, Chupong Ittiwut3, Pichit Siriwan4, Vichai Chichareon5, Kanya Suphapeetiporn1,2, Vorasuk Shotelersuk1,2. 1. 1 Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University , Bangkok, Thailand . 2. 2 Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital , the Thai Red Cross Society, Bangkok, Thailand . 3. 3 Central Laboratory, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University , Bangkok, Thailand . 4. 4 Deputy Director of Relief and Community Health Bureau , the Thai Red Cross Society, Bangkok, Thailand . 5. 5 Department of Surgery, Faculty of Medicine, Prince of Songhla University , HaadYai, Songkla, Thailand .
Abstract
OBJECTIVE: The etiology of oral clefts in humans is genetically complex and mutations in multiple genes have been linked with clefting. CDH1 (E-cadherin) has been found to be involved in lip and palate development, and CDH1 mutations are associated with oral clefts in some populations. MATERIALS AND METHODS: To determine if there is an association between CDH1 and oral clefting in a Thai population, we sequenced the entire 6.5-kb coding region of the CDH1 gene in 80 oral cleft patients and compared the identified variants with those found in 138 unrelated Thai individuals who did not have oral clefts, as genotyped by exome sequencing. RESULTS: Among the oral cleft patients, four nonsynonymous single nucleotide variants (SNVs), c.1235T>C (p.V412A), c.1273G>A (p.V425I), c.1565C>T (p.T522I), and c.1888C>G (p.L630V), were identified. Only one nonsynonymous variant (c.1409C>T; p.T470I) was found among the 138 noncleft exomes. The frequency of nonsynonymous SNVs on the CDH1 gene in oral cleft patients (4/80) was significantly higher than that in the control group (1/138) (p = 0.042). CONCLUSION: We found that nonsynonymous variants of CDH1 were associated with oral clefts in the Thai population.
OBJECTIVE: The etiology of oral clefts in humans is genetically complex and mutations in multiple genes have been linked with clefting. CDH1 (E-cadherin) has been found to be involved in lip and palate development, and CDH1 mutations are associated with oral clefts in some populations. MATERIALS AND METHODS: To determine if there is an association between CDH1 and oral clefting in a Thai population, we sequenced the entire 6.5-kb coding region of the CDH1 gene in 80 oral cleftpatients and compared the identified variants with those found in 138 unrelated Thai individuals who did not have oral clefts, as genotyped by exome sequencing. RESULTS: Among the oral cleftpatients, four nonsynonymous single nucleotide variants (SNVs), c.1235T>C (p.V412A), c.1273G>A (p.V425I), c.1565C>T (p.T522I), and c.1888C>G (p.L630V), were identified. Only one nonsynonymous variant (c.1409C>T; p.T470I) was found among the 138 noncleft exomes. The frequency of nonsynonymous SNVs on the CDH1 gene in oral cleftpatients (4/80) was significantly higher than that in the control group (1/138) (p = 0.042). CONCLUSION: We found that nonsynonymous variants of CDH1 were associated with oral clefts in the Thai population.
Authors: Liza L Cox; Timothy C Cox; Lina M Moreno Uribe; Ying Zhu; Chika T Richter; Nichole Nidey; Jennifer M Standley; Mei Deng; Elizabeth Blue; Jessica X Chong; Yueqin Yang; Russ P Carstens; Deepti Anand; Salil A Lachke; Joshua D Smith; Michael O Dorschner; Bruce Bedell; Edwin Kirk; Anne V Hing; Hanka Venselaar; Luz C Valencia-Ramirez; Michael J Bamshad; Ian A Glass; Jonathan A Cooper; Eric Haan; Deborah A Nickerson; Hans van Bokhoven; Huiqing Zhou; Katy N Krahn; Michael F Buckley; Jeffrey C Murray; Andrew C Lidral; Tony Roscioli Journal: Am J Hum Genet Date: 2018-05-24 Impact factor: 11.025
Authors: Arthavan Selvanathan; Cheng Yee Nixon; Ying Zhu; Luigi Scietti; Federico Forneris; Lina M Moreno Uribe; Andrew C Lidral; Peter A Jezewski; John B Mulliken; Jeffrey C Murray; Michael F Buckley; Timothy C Cox; Tony Roscioli Journal: Genes (Basel) Date: 2020-04-03 Impact factor: 4.096