Whole-Exome Sequencing Identified Two Novel Pathogenic Mutations in the PTCH1 Gene in BCNS
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Published:2023-06-24
Issue:7
Volume:45
Page:5293-5304
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ISSN:1467-3045
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Container-title:Current Issues in Molecular Biology
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language:en
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Short-container-title:CIMB
Author:
Pál Margit12ORCID, Vetró Éva3, Nagy Nikoletta12ORCID, Nagy Dóra14ORCID, Horváth Emese1, Bokor Barbara Anna1, Varga Anita5, Seres László3, Oláh Judit56, Piffkó József3, Széll Márta12
Affiliation:
1. Department of Medical Genetics, University of Szeged, 6720 Szeged, Hungary 2. ELKH-SZTE Functional Clinical Genetics Research Group, Eötvös Loránd Research Network, 6720 Szeged, Hungary 3. Department of Oral and Maxillofacial Surgery, University of Szeged, 6725 Szeged, Hungary 4. Institute of Medical Genetics, Kepler University Hospital Med Campus IV, Johannes Kepler University Linz, 4020 Linz, Austria 5. Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, Hungary 6. Department of Oncotherapy, University of Szeged, 6720 Szeged, Hungary
Abstract
Basal cell nevus syndrome (BCNS, OMIM 109400) is a familial cancer syndrome characterized by the development of numerous basal cell cancers and various other developmental abnormalities, including epidermal cysts of the skin, calcified dural folds, keratocysts of the jaw, palmar and plantar pits, ovarian fibromas, medulloblastomas, lymphomesenteric cysts, and fetal rhabdomyomas. BCNS shows autosomal dominant inheritance and is caused by mutations in the patched 1 (PTCH1) gene and the suppressor of the fused homolog (SUFU) gene. In a few cases, variants of patched 2 (PTCH2) have been found in patients who met the criteria for BCNS. In an investigation of 11 Hungarian families who fulfilled the diagnostic criteria for BCNS, whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) identified two novel pathogenic variants (c.2994C>A; p.Cys998Ter and c.814_818del; p.Asn272SerfsTer11), one recently identified variant (c.1737_1745del p.Val580_Val582del), and three recurrent disease-causing variants of the PTCH1 gene with a diagnosis rate of 63.6%. Disease-causing variants were not found for the SUFU and PTCH2 genes. These applied methods could not fully elucidate the genetic background of all the BCNS cases that we investigated. To uncover the missing heritability of BCNS, whole-genome sequencing or an epigenetic approach might be considered in the future.
Subject
Microbiology (medical),Molecular Biology,General Medicine,Microbiology
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