Identification of a Novel IQCE 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 IQCE gene. More precisely, loss-of-function of IQCE 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 IQCE 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 IQCE genomic regions (DEL:chr7:2606751_2641098) encompassing exons 2-18 of the gene. Conclusion: IQCE 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 IQCE 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.

Automated summary

Non-syndromic polydactyly is associated with pathogenic variants in IQCE gene, and this case report identifies a pathogenic IQCE variant and a large deletion involving IQCE gene using whole-exome sequencing. The IQCE gene codes for a protein that positively regulates the Hedgehog signaling pathway at the base of the primary cilia. This study highlights the importance of using ExomeDepth in routine WES analysis for diagnosing rare genetic diseases.