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A novel splicing mutation of ARHGAP29 is associated with nonsyndromic cleft lip with or without cleft palate

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journal contribution
posted on 24.08.2020, 09:02 authored by Qiuxia Yu, Qiong Deng, Fang Fu, Ru Li, Wenwen Zhang, Junhui Wan, Xin Yang, Dan Wang, Fucheng Li, Shaoqing Wu, Jian Li, Dongzhi Li, Can Liao

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common birth defects, and occurs in approximately 1/700 live births worldwide. The correlation between the ABCA4-ARHGAP29 region and NSCL/P was first identified by genome-wide association studies (GWAS), but few reports have examined NSCL/P caused by ARHGAP29 mutations in the Chinese population.

We performed chromosome microarray analysis (CMA) for two consecutive abnormal fetuses and whole exome sequencing (WES) for the family, including 3 patients and 2 normal family members, Sanger sequencing and RT-PCR were used to confirm the mutation.

We identified a novel splice donor mutation (ARHGAP29 c.1920 + 1G > A) in two consecutive NSCL/P fetuses, and the variant was inherited from the mother and grandfather. The mutation caused abnormal skipping of exon 17, and the mRNA level of ARHGAP29 was significantly decreased compared to the wild type.

In this study, we successfully diagnosed the genetic cause of NSCL/P in a family and first report that the c.1920 + 1G > A mutation in ARHGAP29 is associated with NSCL/P. Our study enriches the genetic landscape of NSCL/P, extends the mutation spectrum of ARHGAP29, and provides a new direction for the diagnosis of NSCL/P in patients and its prenatal diagnosis in fetuses.


This study was supported by the National Natural Science Foundation of China [81671474, 81771594, and 81873836], Natural Science Foundation of Guangdong Province [2017A030313460 and 2019A1515012034], Major Project of the Department of Science and Technology of Guangzhou [201704020108].