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Novel nonsense mutation in MSX 1 causes tooth agenesis with cleft lip in a Chinese family
Author(s) -
Liang Jia,
Zhu Lingling,
Meng Liuyan,
Chen Dong,
Bian Zhuan
Publication year - 2012
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/j.1600-0722.2012.00965.x
Subject(s) - nonsense mutation , mutation , genetics , biology , exon , agenesis , gene , phenotype , microbiology and biotechnology , nonsense , genomic dna , missense mutation
Tooth agenesis is one of the most common developmental disorders in humans. Previous studies have attributed non‐syndromic tooth agenesis to mutations in several genes, including MSX 1 , PAX 9 , EDA , and AXIN 2 . In this study, we investigated a Chinese family with tooth agenesis combined with cleft lip. Genomic DNA was isolated from blood samples of all available family members. Candidate genes MSX 1 and PAX 9 were amplified by the PCR and directly sequenced. A novel heterozygous mutation at c.C565T, exon 2 of MSX 1 , was identified in affected members. To analyze the effect of the nonsense mutation on MSX 1 expression, vectors containing wild‐type and mutated MSX 1 were constructed and transfected into COS 7 cell lines. Real‐time PCR showed that the mRNA expression of the mutated MSX 1 was dramatically reduced compared with that of the wild‐type MSX 1 . Our findings suggest that the nonsense mutation in MSX 1 might have resulted in rapid degradation of the mutated transcript and caused the phenotype of tooth agenesis with cleft lip in the Chinese family.