Yuhua Pan1, Sheng Yi2, Dong Chen3, Xinya Du4, Xinchen Yao1, Fei He5, Fu Xiong6,7,8. 1. School of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 2. Genetic and Metabolic Central Laboratory, Birth Defects Prevention and Control Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, China. 3. Department of Stomatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 4. Department of Stomatology, The People's Hospital of Longhua, 38 Jinglong Jianshe Road, Longhua, Shenzhen, Guangdong, 518109, People's Republic of China. 5. Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, 1838 Guangzhou North Avenue, Guangzhou, 510515, China. 357356772@qq.com. 6. Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, 1838 Guangzhou North Avenue, Guangzhou, 510515, China. xiongfu@smu.edu.cn. 7. Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, Guangdong, China. xiongfu@smu.edu.cn. 8. Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, China. xiongfu@smu.edu.cn.
Abstract
OBJECTIVES: KDF1 is a recently identified gene related to tooth development, but it has been little studied. To date, only three cases have been reported in which KDF1 mutations are related to tooth development, including two ectodermal dysplasia cases accompanied by tooth loss and one non-syndromic case with tooth agenesis. However, no KDF1 mutations have been reported as associated with non-syndromic anodontia. Here, the aim was to investigate the genetic etiology of this condition and explore the functional role of a novel KDF1 mutation in a Chinese patient with non-syndromic anodontia. MATERIALS AND METHODS: Pathogenic variants were identified by whole-exome and Sanger sequencing. Meanwhile, we conducted a literature review of the reported KDF1 mutations and performed an in vitro functional analysis of four anodontia-causing KDF1 mutations (one novel and three known). RESULTS: We identified a novel de novo missense mutation (c.911 T > A, p.I304N) in the KDF1 gene in a Chinese patient with severe non-syndromic anodontia. In vitro functional studies showed altered mRNA and protein expression levels of the mutant KDF1. CONCLUSIONS: Our results are the first report of KDF1 missense mutation causing non-syndromic anodontia. CLINICAL RELEVANCE: This study not only further supports the important role of KDF1 in non-syndromic congenital anodontia, but also expands the spectrum of KDF1 mutations and will contribute to the genetic diagnosis and counselling of families with anodontia.
OBJECTIVES: KDF1 is a recently identified gene related to tooth development, but it has been little studied. To date, only three cases have been reported in which KDF1 mutations are related to tooth development, including two ectodermal dysplasia cases accompanied by tooth loss and one non-syndromic case with tooth agenesis. However, no KDF1 mutations have been reported as associated with non-syndromic anodontia. Here, the aim was to investigate the genetic etiology of this condition and explore the functional role of a novel KDF1 mutation in a Chinese patient with non-syndromic anodontia. MATERIALS AND METHODS: Pathogenic variants were identified by whole-exome and Sanger sequencing. Meanwhile, we conducted a literature review of the reported KDF1 mutations and performed an in vitro functional analysis of four anodontia-causing KDF1 mutations (one novel and three known). RESULTS: We identified a novel de novo missense mutation (c.911 T > A, p.I304N) in the KDF1 gene in a Chinese patient with severe non-syndromic anodontia. In vitro functional studies showed altered mRNA and protein expression levels of the mutant KDF1. CONCLUSIONS: Our results are the first report of KDF1 missense mutation causing non-syndromic anodontia. CLINICAL RELEVANCE: This study not only further supports the important role of KDF1 in non-syndromic congenital anodontia, but also expands the spectrum of KDF1 mutations and will contribute to the genetic diagnosis and counselling of families with anodontia.
Authors: E M Santos; J F R Paula; P M C Motta; M B Heinemann; R C Leite; J P A Haddad; H L Del Puerto; J K P Reis Journal: Genet Mol Res Date: 2010-08-17
Authors: Hanan E Shamseldin; Ola Khalifa; Yousef M Binamer; Abdulmonem Almutawa; Stefan T Arold; Hamad Zaidan; Fowzan S Alkuraya Journal: Hum Genet Date: 2016-11-12 Impact factor: 4.132
Authors: Marie-José van den Boogaard; Marijn Créton; Yvon Bronkhorst; Annemieke van der Hout; Eric Hennekam; Dick Lindhout; Marco Cune; Hans Kristian Ploos van Amstel Journal: J Med Genet Date: 2012-05 Impact factor: 6.318
Authors: Alessandro Salvi; Edoardo Giacopuzzi; Elena Bardellini; Francesca Amadori; Lia Ferrari; Giuseppina De Petro; Giuseppe Borsani; Alessandra Majorana Journal: Int J Mol Med Date: 2016-09-19 Impact factor: 4.101