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A novel PTCH 1 mutation underlies nonsyndromic cleft lip and/or palate in a Han Chinese family
Author(s) -
Zhao Huaxiang,
Zhong Wenjie,
Leng Chuntao,
Zhang Jieni,
Zhang Mengqi,
Huang Wenbin,
Zhang Yunfan,
Li Weiran,
Jia Peizeng,
Lin Jiuxiang,
Maimaitili Gulibaha,
Chen Feng
Publication year - 2018
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12915
Subject(s) - missense mutation , genetics , sanger sequencing , biology , ptch1 , exome sequencing , mutation , mendelian inheritance , proband , exon , gene , sonic hedgehog
Objectives Cleft lip and/or palate ( CL /P) is the most common craniofacial congenital disease, and it has a complex aetiology. This study aimed to identify the causative gene mutation of a Han Chinese family with CL /P. Subjects and Methods Whole exome sequencing was conducted on the proband and her mother, who exhibited the same phenotype. A Mendelian dominant inheritance model, allele frequency, mutation regions, functional prediction and literature review were used to screen and filter the variants. The candidate was validated by Sanger sequencing. Conservation analysis and homology modelling were conducted. Results A heterozygous missense mutation c.1175C>T in the PTCH 1 gene predicting p.Ala392Val was identified. This variant has not been reported and was predicted to be deleterious. Sanger sequencing verified the variant and the dominant inheritance model in the family. The missense alteration affects an amino acid that is evolutionarily conserved in the first extracellular loop of the PTCH 1 protein. The local structure of the mutant protein was significantly altered according to homology modelling. Conclusions Our findings suggest that c.1175C>T in PTCH 1 ( NM_000264 ) may be the causative mutation of this pedigree. Our results add to the evidence that PTCH 1 variants play a role in the pathogenesis of orofacial clefts.