UIP HEALTH MED., 2016, 1(1) doi: http://dx.doi.org/10.7454/uiphm.v1i0.37 108 PAX9 Mutation of Non-Syndromic Hypodontia in a Malaysian Family Nur Farahiyah Mohamed Idrus , Nur Syahira Rosley, Nining Irfanita, Yunita Dewi Ardini Fadjar, Solachuddin J.A Ichwan, Widya Lestari * Kulliyyah of Dentistry, International Islamic University Malaysia, Kuantan, 25200, Malaysia *E-mail: drwidya@iium.edu.my Abstract Objective: Hypodontia is portrayed by the missing of one to six numbers of teeth. PAX9 is one of the genes that caused non-syndromic hypodontia. We aimed to investigate the PAX9 mutation of non-syndromic hypodontia with clinical variability in a Malaysian hypodontia family. Methods: Clinical examinations for all participants whilst orthophantomogram (OPG) was taken for hypodontia patient only. Saliva was collected for genetic analysis. Direct sequencing was performed by using exon 2and 3 of PAX9 gene. Results: 3 out of 5 family members are affected with hypodontia. The mother has missing posterior tooth and her daughters have missing anterior teeth. The point mutation was identified on exon 2 on patient 1C; c.620G>T and on exon 3 on patients 1B; c.465delG, 1C; c.273T>G, 1D; c.462delT. Conclusions: Our findings suggested those identified points mutations of PAX9 either on exon 2 or exon 3 is responsible for the hypodontia phenotype in this family. Keywords: hypodontia, mutation, PAX9 Introduction Hypodontia is one of the most common dental anomalies, characterized by missing one to six teeth in the mouth. This anomaly can be caused by the environmental factors or genetic. It has been identified as both non-syndromic and syndromic. The non-syndromic form of hypodontia can be sporadic or familial. 1 Familial tooth agenesis can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. To date it has been demonstrated MSX! And PAX9 are responsible for familial and sporadic hypodontia. Previously, in animal based- studies have revealed that MSX1 and PAX9 knockout mice induced an arrest in tooth formation at the bud stages. Among them, PAX9 was more intensively studied. PAX9 is a transcription factor that is express in dental mesenchyme at initiation, bud, cap and bell stages of odontogenesis. 3 The prevalence of hypodontia in Malaysian was (2.8%) and it is considered as high. 4 While much progress has been made in understanding the developmental basis of the tooth formation, knowledge of the aetiological basis of inherited tooth loss remain poor especially in Malaysian hypodontia families. Materials and Methods Research ethic approval Ethical approval was obtained for this study from Research Ethic Committee of the International Islamic University Malaysia (IREC-342). Family selection and pedigree construction The proband whom was selected randomly attending Dental Polyclinic International Islamic University Malaysia, Kuantan, Pahang, Malaysia. All participants are Malaysian descent. The proband and the family members including siblings and parents (first degree relatives only) were invited to participate in this study. All of medical information related to hypodontia such as birth defect, trauma and radiations were gathered. Full dental charting was done to locate the missing tooth. Tooth agenesis was characterized by orthopantomogram (OPG) and careful examination of their clinical charts. Those non hypodontia family members were included as our control group. DNA collection, screening and mutational analysis Methods that have been used are described by Paixao- Cortes et al with slightly modifications. A non-invasive method was used to collect patient’s deoxyribonucleotides (DNA) where by a 2ml of saliva was collected from each of participants. Then, genomic DNA will be extracted from saliva using the QIAamp sample DNA MiniKit