EDA mutation screening and phenotype analysis in patients with tooth agenesis / 北京大学学报(医学版)

ABSTRACT

Objective:To screen the ectodysplasin A (EDA)gene mutation in the patients with non-syndromic tooth agenesis and ectodermal dysplasia,and to analyze the phenotype of missing teeth pattern in these two groups of patients.Methods:In the study,174 patients with tooth agenesis (143non-syn-dromic,31ectodermal dysplasia)and 451 health control volunteers were enrolled from the clinic,and the genome DNA was extracted from either peripheral blood or oral mucosal swab.The coding region of EDA gene was then amplified by PCR,sequenced and blasted to online NCBI database.The missing teeth were recorded for all patients,and the missing teeth from patients with EDA mutation were com-pared among the different dentition sites.Results:33 patients were identified with EDA mutation.In the non-syndromic patients,13 /143(9.09%)were identified with EDA mutation,while in patients with ec-todermal dysplasia,20 /31 (64.52%)were found with EDA mutation.Ten novel EDA mutations were identified (c.769G >C[p.G257R],c.936C >G[p.I312M],c.223G >A[p.E75K],c.1166C >T[p. P389L],c.133G >C[p.G45R],c.1109G >A[p.E370K],c.914G >T[p.S305I],c.916C >T[p. Q306X],c.602G >T[p.G201V],c.88 -89insG[p.A30GfsX69]).For each dentition site there was no statistic difference in the number of missing teeth between the left and right sides,so the number from both sides were combined later in the analysis.In the patients with EDA mutation,the non-syndromic pa-tients had fewer missing teeth (15.9 ±6.4 missing teeth for each,207 /364 in total)than the patients with ectodermal dysplasia (23.9 ±4.3,478 /560).In the non-syndromic patients with EDA mutation, the maxillay central incisors and first molars were less affected,with the same missing rate as 19.2% (5 /26).While the mandibular central incisors (with a missing rate of 76.9%,20 /26),the maxillary late-ral incisors (the missing rate88.5%,23 /26 ),the mandibular lateral incisors (the missing rate80.8%,21 /26),and the maxillary first premolars (the missing rate80.8%,21 /26)were more likely to be missing.In the ectodermal dysplasia patients with EDA mutation,only maxillary central incisors (the missing rate60%,24 /40),maxillary canines (the missing rate70%,28 /40),mandibular ca-nines (the missing rate67.5%,27 /40),maxillary first molars (the missing rate65%,26 /40)and mandibular first molars (the missing rate72.5%,29 /40)had higher possibility of persistence.Teeth at other dentition sites were more likely to be affected (the minimum missing rate87.5%,35 /40). Conclusion:The findings would help to reveal the EDA gene and its function in ectodermal organogene-sis.