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DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases

Introduction: The increasing usage of NGS technology has enabled the discovery of new causal genes in ciliopathies, including the DCDC2 gene. The aim of our study was to present the clinical, pathological and molecular report of six patients (from three unrelated families) with DCDC2 biallelic patho...

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Autores principales: Lipiński, Patryk, Ciara, Elżbieta, Jurkiewicz, Dorota, Mekrouda, Magda, Cielecka-Kuszyk, Joanna, Jurkiewicz, Elżbieta, Płoski, Rafał, Pawłowska, Joanna, Jankowska, Irena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252754/
https://www.ncbi.nlm.nih.gov/pubmed/37296768
http://dx.doi.org/10.3390/diagnostics13111917
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author Lipiński, Patryk
Ciara, Elżbieta
Jurkiewicz, Dorota
Mekrouda, Magda
Cielecka-Kuszyk, Joanna
Jurkiewicz, Elżbieta
Płoski, Rafał
Pawłowska, Joanna
Jankowska, Irena
author_facet Lipiński, Patryk
Ciara, Elżbieta
Jurkiewicz, Dorota
Mekrouda, Magda
Cielecka-Kuszyk, Joanna
Jurkiewicz, Elżbieta
Płoski, Rafał
Pawłowska, Joanna
Jankowska, Irena
author_sort Lipiński, Patryk
collection PubMed
description Introduction: The increasing usage of NGS technology has enabled the discovery of new causal genes in ciliopathies, including the DCDC2 gene. The aim of our study was to present the clinical, pathological and molecular report of six patients (from three unrelated families) with DCDC2 biallelic pathogenic variants. A detailed overview of the reported patients with DCDC2-related disease was provided. Material and methods: A retrospective chart review of the clinical, biochemical, pathological (liver histology) and molecular features of the study group was performed. The database PubMed (MEDLINE) was searched for relevant studies. Results: All the patients presented with cholestatic jaundice and elevated GGT; the mean age was 2 months. The initial liver biopsy was performed in four children at a mean age of 3 months (age range: 2–5 months). In all of them, features of cholestasis, portal fibrosis and mild portal inflammation were observed; in three of them ductular proliferation was observed. One patient had undergone liver transplantation (LTx) at 8 years of age. At hepatectomy, a biliary-pattern cirrhosis was observed. Only one patient presented with features of renal disease. Whole exome sequencing was performed in all patients at the last follow-up visit (mean age 10 years). Three different variants (one novel) in the DCDC2 gene were identified in the study group. With our six patients, a total of 34 patients with DCDC2-related hepatic ciliopathy were identified. The main clinical presentation of DCDC2-related ciliopathy was liver disease in the form of neonatal sclerosing cholangitis. The predominance of early and severe liver disease associated with no or mildly expressed kidney involvement was observed. Conclusions: Our findings expand the molecular spectrum of pathogenic DCDC2 variants, provide a more accurate picture of the phenotypic expression associated with molecular changes in this gene and confirm a loss of functional behaviour as the mechanism of disease.
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spelling pubmed-102527542023-06-10 DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases Lipiński, Patryk Ciara, Elżbieta Jurkiewicz, Dorota Mekrouda, Magda Cielecka-Kuszyk, Joanna Jurkiewicz, Elżbieta Płoski, Rafał Pawłowska, Joanna Jankowska, Irena Diagnostics (Basel) Article Introduction: The increasing usage of NGS technology has enabled the discovery of new causal genes in ciliopathies, including the DCDC2 gene. The aim of our study was to present the clinical, pathological and molecular report of six patients (from three unrelated families) with DCDC2 biallelic pathogenic variants. A detailed overview of the reported patients with DCDC2-related disease was provided. Material and methods: A retrospective chart review of the clinical, biochemical, pathological (liver histology) and molecular features of the study group was performed. The database PubMed (MEDLINE) was searched for relevant studies. Results: All the patients presented with cholestatic jaundice and elevated GGT; the mean age was 2 months. The initial liver biopsy was performed in four children at a mean age of 3 months (age range: 2–5 months). In all of them, features of cholestasis, portal fibrosis and mild portal inflammation were observed; in three of them ductular proliferation was observed. One patient had undergone liver transplantation (LTx) at 8 years of age. At hepatectomy, a biliary-pattern cirrhosis was observed. Only one patient presented with features of renal disease. Whole exome sequencing was performed in all patients at the last follow-up visit (mean age 10 years). Three different variants (one novel) in the DCDC2 gene were identified in the study group. With our six patients, a total of 34 patients with DCDC2-related hepatic ciliopathy were identified. The main clinical presentation of DCDC2-related ciliopathy was liver disease in the form of neonatal sclerosing cholangitis. The predominance of early and severe liver disease associated with no or mildly expressed kidney involvement was observed. Conclusions: Our findings expand the molecular spectrum of pathogenic DCDC2 variants, provide a more accurate picture of the phenotypic expression associated with molecular changes in this gene and confirm a loss of functional behaviour as the mechanism of disease. MDPI 2023-05-30 /pmc/articles/PMC10252754/ /pubmed/37296768 http://dx.doi.org/10.3390/diagnostics13111917 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lipiński, Patryk
Ciara, Elżbieta
Jurkiewicz, Dorota
Mekrouda, Magda
Cielecka-Kuszyk, Joanna
Jurkiewicz, Elżbieta
Płoski, Rafał
Pawłowska, Joanna
Jankowska, Irena
DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases
title DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases
title_full DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases
title_fullStr DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases
title_full_unstemmed DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases
title_short DCDC2-Related Ciliopathy: Report of Six Polish Patients, Novel DCDC2 Variant, and Literature Review of Reported Cases
title_sort dcdc2-related ciliopathy: report of six polish patients, novel dcdc2 variant, and literature review of reported cases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252754/
https://www.ncbi.nlm.nih.gov/pubmed/37296768
http://dx.doi.org/10.3390/diagnostics13111917
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