Comparative analysis of rare EDAR mutations and tooth agenesis pattern in EDAR ‐ and EDA ‐associated nonsyndromic oligodontia

Autor: Tao Cai, Miao Yu, Hong Qu, Liutao Zhang, Jinglei Zheng, Yang Liu, Dong Han, Yongsheng Zhou, Haochen Liu, Hailan Feng, Sing-Wai Wong, Zhuangzhuang Fan
Rok vydání: 2020
Předmět:
Zdroj: Human Mutation. 41:1957-1966
ISSN: 1098-1004
1059-7794
Popis: Nonsyndromic oligodontia is a rare congenital anomaly. Mutations in the ectodysplasin A receptor (EDAR) gene are the primary cause of hypohidrotic ectodermal dysplasia but are rarely reported in nonsyndromic oligodontia. This study investigated EDAR mutations in multiplex nonsyndromic oligodontia and comparatively analyzed the EDAR- and EDA-related tooth agenesis patterns. Mutation screening was carried out using whole-exome sequencing and familial segregation. Evolutionary conservation and conformational analyses were used to evaluate the potential pathogenic influence of EDAR mutants. EDAR mutations were found to occur in 10.7% of nonsyndromic oligodontia cases. We reported seven heterozygous mutations of EDAR, including five novel mutations (c.404G>A, c.871G>A, c.43G>A, c.1072C>T, and c.1109T>C) and two known mutations (c.319A>G and c.1138A>C). Genotype-phenotype correlation analysis demonstrated that the EDAR-related tooth agenesis pattern was markedly different from EDA. The mandibular second premolars were most frequently missing (57.69%) in EDAR-mutated patients. Our results provide new evidence for the genotypic study of nonsyndromic oligodontia and suggest that EDAR haploinsufficiency results in nonsyndromic tooth agenesis. Furthermore, the distinct pattern between EDAR- and EDA-related tooth agenesis can be used as a guide for mutation screening during the clinical genetic diagnosis of this genetic disorder.
Databáze: OpenAIRE
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