Identification of a Novel Large Deletion through Copy Number Variant Analysis from Whole-Exome Sequencing Data of a Patient with Postaxial Polydactyly Type A7.

INTRODUCTION

Non-syndromic polydactyly has been associated with pathogenic variants in 11 genes until today, including gene. More precisely, loss-of-function of is associated with the autosomal recessive disorder postaxial polydactyly type A7 (PAPA7, MIM #617642).

CASE PRESENTATION

A 3-year-old female patient was referred to our genetics department with postaxial polydactyly, syndactyly, brachydactyly, and hypoplastic teeth. Through whole-exome sequencing (WES), a pathogenic variant was identified (c.895_904del) in the homozygous state, which adequately explained the disease phenotype of our patient. However, copy number variant (CNV) analysis from WES data, using ExomeDepth, revealed a novel, likely pathogenic large deletion involving genomic regions (DEL:chr7:2606751_2641098) encompassing exons 2-18 of the gene.

CONCLUSION

gene codes for a 695-amino acid protein located at the base of the primary cilia that positively regulates the Hedgehog signaling pathway. This case report represents the first description of a large deletion in and indicates that implementation of ExomeDepth in routine WES analysis can contribute valuable information toward elucidating the correct etiology of rare genetic diseases, increasing the diagnostic yield, and minimizing the need for additional tests.