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.
| Title: | 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. |
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| Authors: | Tilemis FN; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Research University Institute for the Study and Prevention of Genetic and Malignant Disease of Childhood, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Marinakis NM; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Research University Institute for the Study and Prevention of Genetic and Malignant Disease of Childhood, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Kosma K; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Fostira F; Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research 'Demokritos', Athens, Greece.; Traeger-Synodinos J; Laboratory of Medical Genetics, St. Sophia's Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. |
| Source: | Molecular syndromology [Mol Syndromol] 2023 Jun; Vol. 14 (3), pp. 225-230. Date of Electronic Publication: 2023 Jan 13. |
| Publication Type: | Case Reports; Journal Article |
| Language: | English |
| Journal Info: | Publisher: S. Karger Country of Publication: Switzerland NLM ID: 101525192 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1661-8769 (Print) Linking ISSN: 16618769 NLM ISO Abbreviation: Mol Syndromol Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Basel : S. Karger |
| Abstract: | 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.; (Copyright © 2023 by S. Karger AG, Basel.) |
| Competing Interests: | The authors declare no conflict of interest. |
| References: | Bioinformatics. 2012 Nov 1;28(21):2747-54. (PMID: 22942019); Am J Med Genet A. 2021 Aug;185(8):2561-2571. (PMID: 34008892); Eur J Hum Genet. 2020 Dec;28(12):1645-1655. (PMID: 32561899); Genet Med. 2015 May;17(5):405-24. (PMID: 25741868); Hum Mutat. 2020 Jan;41(1):240-254. (PMID: 31549751); Front Genet. 2021 Oct 15;12:746949. (PMID: 34721536); Genet Med. 2021 Nov;23(11):2230. (PMID: 33731880); Nucleic Acids Res. 2018 Jul 2;46(W1):W545-W553. (PMID: 29860484); PLoS One. 2018 Dec 17;13(12):e0209185. (PMID: 30557390); Dev Cell. 2014 Mar 10;28(5):483-96. (PMID: 24582806); Eur J Hum Genet. 2017 Aug;25(8):960-965. (PMID: 28488682); PLoS One. 2017 Mar 27;12(3):e0174206. (PMID: 28346501); Front Genet. 2018 Nov 06;9:447. (PMID: 30459804); Bosn J Basic Med Sci. 2018 Feb 20;18(1):8-20. (PMID: 29274272); J Dent Res. 2017 Aug;96(9):965-974. (PMID: 28605602); J Dent Res. 2013 Mar;92(3):222-8. (PMID: 23315474); J Dent Res. 2014 May;93(5):475-82. (PMID: 24659776); Bioinformatics. 2019 Jun 1;35(11):1978-1980. (PMID: 30376034); Int J Mol Sci. 2018 Aug 03;19(8):. (PMID: 30081498) |
| Contributed Indexing: | Keywords: Copy number variant; ExomeDepth; Hypoplastic teeth; IQCE; Postaxial polydactyly; Whole-exome sequencing |
| Entry Date(s): | Date Created: 20230616 Latest Revision: 20231202 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10267488 |
| DOI: | 10.1159/000527777 |
| PMID: | 37323200 |
| Database: | MEDLINE |
Case Reports; Journal Article