Candidate gene analysis of tooth agenesis identifies novel mutations in six genes and suggests significant role for WNT and EDA signaling and allele combinations.

[oligodontia]

Failure to develop complete dentition , tooth agenesis , is a common developmental anomaly manifested most often as isolated but also as associated with many developmental syndromes . It typically affects third molars or one or few other permanent teeth but severe agenesis is also relatively prevalent . Here we report mutational analyses of seven candidate genes in a cohort of 127 probands with non-syndromic tooth agenesis . 82 lacked more than five permanent teeth excluding third molars , called as oligodontia . We identified 28 mutations , 17 of which were novel . Together with our previous reports , we have identified two mutations in MSX 1 , AXIN 2 and EDARADD , five in PAX 9 , four in EDA and EDAR , and nine in WNT 10 A . They were observed in 58 probands (44 %), with a mean number of missing teeth of 11 .7 (range 4 to 34 ). Almost all of these probands had severe agenesis . Only few of the probands but several relatives with heterozygous genotypes of WNT 10 A or EDAR conformed to the common type of non-syndromic tooth agenesis , incisor-premolar hypodontia . Mutations in MSX 1 and PAX 9 affected predominantly posterior teeth , whereas both deciduous and permanent incisors were especially sensitive to mutations in EDA and EDAR . Many mutations in EDAR , EDARADD and WNT 10 A were present in several families . Biallelic or heterozygous genotypes of WNT 10 A were observed in 32 and hemizygous or heterozygous genotypes of EDA , EDAR or EDARADD in 22 probands . An EDARADD variant were in seven probands present together with variants in EDAR or WNT 10 A , suggesting combined phenotypic effects of alleles in distinct genes .

Diseases
Validation

Diseases presenting "common developmental" symptom

dentinogenesis imperfecta

oligodontia

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