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Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser))

Generalized Arterial Calcification of Infancy (GACI) is a rare disease inherited in a recessive manner, with severe and diffuse early onset of calcifications along the internal elastic lamina in large and medium size arteries. The diagnosis results are from clinical manifestations, imaging, histopat...

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Autores principales: Bulfamante, Gaetano Pietro, Carpenito, Laura, Bragantini, Emma, Graziani, Silvia, Bellizzi, Maria, Bagowski, Christoph Peter, Shoukier, Moneef, Rivieri, Francesca, Soffiati, Massimo, Barbareschi, Mattia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229691/
https://www.ncbi.nlm.nih.gov/pubmed/34199854
http://dx.doi.org/10.3390/diagnostics11061034
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author Bulfamante, Gaetano Pietro
Carpenito, Laura
Bragantini, Emma
Graziani, Silvia
Bellizzi, Maria
Bagowski, Christoph Peter
Shoukier, Moneef
Rivieri, Francesca
Soffiati, Massimo
Barbareschi, Mattia
author_facet Bulfamante, Gaetano Pietro
Carpenito, Laura
Bragantini, Emma
Graziani, Silvia
Bellizzi, Maria
Bagowski, Christoph Peter
Shoukier, Moneef
Rivieri, Francesca
Soffiati, Massimo
Barbareschi, Mattia
author_sort Bulfamante, Gaetano Pietro
collection PubMed
description Generalized Arterial Calcification of Infancy (GACI) is a rare disease inherited in a recessive manner, with severe and diffuse early onset of calcifications along the internal elastic lamina in large and medium size arteries. The diagnosis results are from clinical manifestations, imaging, histopathologic exams, and genetic tests. GACI is predominantly caused by biallelic pathogenic variant in the ENPP1 gene (GACI1, OMIM#208000) and, to a lesser extent, by pathogenic variants in the ABCC6 gene (GACI2, OMIM#614473). We present a novel variation in the ENPP1 gene identified in a patient clinically diagnosed with GACI and confirmed by genetic investigation and autopsy as GACI type 1. The sequence analysis of the patient’s ENPP1 gene detected two heterozygous variants c.1412A>G (p.Tyr471Cys) and c.1715T>C (p.Leu572Ser). The variant c.1715T>C (p.Leu572Ser) has not been described yet in the literature and in mutation databases. A genetic analysis was also carried out for the parents of the newborn; the heterozygous pathogenic variant c.1412A>G (p.Tyr471Cys) was detected in the mother’s ENPP1 gene, and a sequence analysis of the father’s ENPP1 gene revealed the novel heterozygous variant c.1715T>C (p.Leu572Ser). Our results showed that the variant c.1715T>C (p.Leu572Ser) may have a pathogenic role in the development of GACI type1 (GACI1, OMIM#208000), at least when associated with the pathogenic c.1412A>G (p.Tyr471Cys) variant. The identification of novel mutations potentially enabled genotype/phenotype associations that will ultimately have an impact on clinical management and prognosis for the disease.
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spelling pubmed-82296912021-06-26 Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser)) Bulfamante, Gaetano Pietro Carpenito, Laura Bragantini, Emma Graziani, Silvia Bellizzi, Maria Bagowski, Christoph Peter Shoukier, Moneef Rivieri, Francesca Soffiati, Massimo Barbareschi, Mattia Diagnostics (Basel) Article Generalized Arterial Calcification of Infancy (GACI) is a rare disease inherited in a recessive manner, with severe and diffuse early onset of calcifications along the internal elastic lamina in large and medium size arteries. The diagnosis results are from clinical manifestations, imaging, histopathologic exams, and genetic tests. GACI is predominantly caused by biallelic pathogenic variant in the ENPP1 gene (GACI1, OMIM#208000) and, to a lesser extent, by pathogenic variants in the ABCC6 gene (GACI2, OMIM#614473). We present a novel variation in the ENPP1 gene identified in a patient clinically diagnosed with GACI and confirmed by genetic investigation and autopsy as GACI type 1. The sequence analysis of the patient’s ENPP1 gene detected two heterozygous variants c.1412A>G (p.Tyr471Cys) and c.1715T>C (p.Leu572Ser). The variant c.1715T>C (p.Leu572Ser) has not been described yet in the literature and in mutation databases. A genetic analysis was also carried out for the parents of the newborn; the heterozygous pathogenic variant c.1412A>G (p.Tyr471Cys) was detected in the mother’s ENPP1 gene, and a sequence analysis of the father’s ENPP1 gene revealed the novel heterozygous variant c.1715T>C (p.Leu572Ser). Our results showed that the variant c.1715T>C (p.Leu572Ser) may have a pathogenic role in the development of GACI type1 (GACI1, OMIM#208000), at least when associated with the pathogenic c.1412A>G (p.Tyr471Cys) variant. The identification of novel mutations potentially enabled genotype/phenotype associations that will ultimately have an impact on clinical management and prognosis for the disease. MDPI 2021-06-04 /pmc/articles/PMC8229691/ /pubmed/34199854 http://dx.doi.org/10.3390/diagnostics11061034 Text en © 2021 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
Bulfamante, Gaetano Pietro
Carpenito, Laura
Bragantini, Emma
Graziani, Silvia
Bellizzi, Maria
Bagowski, Christoph Peter
Shoukier, Moneef
Rivieri, Francesca
Soffiati, Massimo
Barbareschi, Mattia
Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser))
title Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser))
title_full Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser))
title_fullStr Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser))
title_full_unstemmed Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser))
title_short Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser))
title_sort generalized arterial calcification of infancy type 1 (gaci1): identification of a novel pathogenic variant (c.1715t>c (p.leu572ser))
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229691/
https://www.ncbi.nlm.nih.gov/pubmed/34199854
http://dx.doi.org/10.3390/diagnostics11061034
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