A Novel Missense Mutation in NALCN Cause CLIFAHDD Syndrome and Prenatal Diagnosis in China

Abstract Background: CLIFAHDD is caused by mutation in NALCN and characterized by facial malformation, hypotonia, and developmental delay. Recently rare mutations in NALCN associated with of CLIFAHDD syndrome have been reported. Methods: Whole exome sequencing (WES) was applied to a diagnosis suspected CLIFAHDD syndrome proband based on clinical symptoms. Blood samples were taken from the parents of the proband for co-segregation analysis using Sanger sequencing. In addition, prenatal gene diagnosis was performed to the family. Finally bioinformatics analysis was utilized to predict the pathogenesis of novel variant. Result: We reported a 24-hour-old proband with a novel missense variant c.3016G>T (p.Val1006Phe) in NALCN by WES. The proband showed clinical symptoms of head abnormalities, neck shortage, thumbs adduction, positional foot deformities and elbows contracture. Prenatal diagnosis revealed that the proband’s sibling did not carry c.3016G>T. Conclusion: Our findings indicate c.3016G>T is a novel pathogenic mutation, while extending new phenotype CLIFAHDD syndrome and enriching the mutation spectrum of the NALCN gene.