Study On The Disease-Causing Genes For The Two Types Of Mongolian Dental Developmental Disorders

Dentinogenesis Imperfect (DGI, MIM,#125490) is an autosomal dominant inherited disease, whose penetrance is 100% and population risk is 1/8000. The patients present the dentinal developmental defect and abnormal dental mineralization. It is classified into three types. The pathogenesis of Dentinogenesis Imperfecta typeâ… (DGI-â… ) is Osteogenesis Imperfecta (OI, MIM,#166240) and patients'oral manifestations are similar to those with Dentinogenesis Imperfecta typeâ…¡(DGI-â…¡, MIM,#125490). The gene mutation of collagen typeâ… is responsible for it. DGI-â…¡or hereditary opalescent dentin is a singly dentinal developmental anomaly. Dentinogenesis Imperfecta typeâ…¢(DGI-â…¢, MIM, #125500) is also called Brandy-type Dentinogenesis Imperfecta or isolate hereditary opalescent dentin, which only happens to 3 isolated ethnic groups.Disease-causing gene of Dentinogenesis Imperfecta typeâ…¡is located on 4q21. A group of genes in this domain, such as DSPP, DMP1, SPP1, BSP and MEPE (OF45), are candidate genes for DGI and relevant to the dental and osseous formations.The studied objects with DGI-â…¡in this research were from a large Mongolian family, whose disease-causing genes were located, isolated and identified systematically with clinical, physiological and biochemical, and molecular biological methods. The result showed that the adenine mononucleotide adjacent to the clipping donor site of third exon and third Intron was replaced by guanosine monophosphate in patients'gene DSPP, namely the transformation of A to G. The normal nucleotide sequence GTGT changed into GTAT. The alteration was not determined in the genes of the normal family members and ones in control group, which indicated that the gene mutation was the cause of DGI-â…¡in the Mongolian family.Ectodermal Agenesia (EDA) is a congenital genetic disease, which is characterized by the agenesia or anomalad of ectoderm-originating tissue, such as hair, sweat gland and tooth and its population risk is approximately one hundred thousandth. Its characteristic clinical manifestations (triple-symptom complex) include hypohidrosis or anhidrosis, sparse hair or hairlessness and dental absence or paramorphia. Its population phenotype and genotype present variable alloplastic. EDA is X-linked recessive inheritance, whose clinical symptoms is more severe for the male patients and phenotype is typical. Female carriers usually have no obvious or less changeable phenotype.Disease-causing gene of EDA is located on Xp12-13.1 of the short arm of X chromosome, called EDA,EDAR and EDARADD. The protein coded by the gene EDA belongs to tumor necrosis factor (TNF) ligand family, but the proteins coded by the gene EDAR and EDARADD are part of TNF receptor family. A lot of research data verify that the gene EDA is prone to mutate. So far nearly its one hundred variants have been reported, which range from the exon and intron 1 to 9 and result in the functional changes of the proteins coded by the gene EDA.The results of our research demonstrated that the clinical symptoms of Mongolian EDA involved dental absence and paramorphia, thick and curly hair and sweating, whose phenotype was different from that reported by the researchers both at home and abroad. The gene sequencing showed the transversion of first exon 193C to G in the probands and patients compared with Genbank, which led to the conversion of normal genetic code CGC to GGC and the replacement of arginine in the location 65 by glycine. The genotype of the mothers of the carriers and other carriers was heterozygous type C/G. The base sequence in the first exon for the normal family members and those in control group was identical to that in GenBank, which indicated that the mutation caused Mongolian EDA and was malgenic.