A Novel EDAR Missense Mutation Identified by Whole Exome Sequencing with
Non-Syndromic Tooth Agenesis in a Chinese Family
Abstract
To investigate novel mutations of pathogenic genes responsible for
non-syndromic tooth agenesis (NSTA) and to provide a genetic basis for
the study of its pathogenesis. Peripheral blood samples of four
pedigrees with NSTA were collected for DNA extraction. The coding region
of the EDA1 gene was amplified by PCR and sequenced to investigate new
mutations. Whole exome sequencing and Sanger sequencing were then
performed for Family 4. A novel mutation c.338G>A
(Cys113Tyr) in the EDAR gene was identified in a pedigree. In addition,
three EDA1 mutations were identified in three patients:
c.865C>T (Arg289Cys), c.866G>A (Arg289His),
and c.1013C>T (Thr338Met). Genotype-phenotype correlation
analysis of EDAR gene mutation showed that NSTA patients were most
likely to lose the maxillary lateral incisors, and the maxillary first
premolars were the least affected. The phenotype of mutations at codon
289 of EDA1 in NSTA reported patients were characterized by lateral
incisors loss, rarely affecting the maxillary first molars. A novel EDAR
missense mutation, c.338G>A (Cys113Tyr), was identified in
a pedigree with NSTA, extending the mutation spectrum of the EDAR gene.
Genotype-phenotype correlation analyses of EDAR and EDA1 mutation could
help to improve disease status prediction in NSTA families.