Case report: A Non-sense mutation (p.Q417*) located in transactivation domain is Responsible for Campomelic Dysplasia.

BACKGROUND

Campomelic dysplasia (CD) is an autosomal dominant skeletal dysplasia syndrome characterized by shortness and bowing of lower extremities, and often accompanied by XY sex reversal. Heterozygous pathogenic variants of or rearrangement involving the long arm of chromosome 17 are the causes of disease. However, evidence for pathogenesis of haploinsufficiency is insufficient.

METHODS

We enrolled a Chinese family where the fetus was diagnosed with CD. The affected fetus was selected for whole-exome sequencing to identify the pathogenic mutations in this family.

RESULTS

After data filtering, a novel non-sense variant (NM_000346.3; c.1249C > T; p.Q417*) was identified as the pathogenic lesion in the fetus. Further co-segregation analysis using Sanger sequencing confirmed that this novel mutation (c.1249C > T; p.Q417*) was a mutation in the affected fetus. This terminated codon mutation identified by bioinformatics was located at an evolutionarily conserved site of . The bioinformatics-based analysis predicted this variant was pathogenic and affected transactivation activity.

CONCLUSION

CD is a rare condition, which connected with tightly. We identified a novel heterozygous variant (p.Q417*) in a Chinese CD family. Our study supports the putative reduced transactivation of variants in the pathogenicity of CD.