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

BACKGROUND

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 region and NSCL/P was first identified by genome-wide association studies (GWAS), but few reports have examined NSCL/P caused by mutations in the Chinese population.

METHODS

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.

RESULTS

We identified a novel splice donor mutation ( 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 was significantly decreased compared to the wild type.

CONCLUSIONS

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 is associated with NSCL/P. Our study enriches the genetic landscape of NSCL/P, extends the mutation spectrum of , and provides a new direction for the diagnosis of NSCL/P in patients and its prenatal diagnosis in fetuses.