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Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family

Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, e...

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Autores principales: Gilis-Januszewska, Aleksandra, Bogusławska, Anna, Hasse-Lazar, Kornelia, Jurecka-Lubieniecka, Beata, Jarząb, Barbara, Sowa-Staszczak, Anna, Opalińska, Marta, Godlewska, Magdalena, Grochowska, Anna, Skalniak, Anna, Hubalewska-Dydejczyk, Alicja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067145/
https://www.ncbi.nlm.nih.gov/pubmed/33807230
http://dx.doi.org/10.3390/genes12040512
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author Gilis-Januszewska, Aleksandra
Bogusławska, Anna
Hasse-Lazar, Kornelia
Jurecka-Lubieniecka, Beata
Jarząb, Barbara
Sowa-Staszczak, Anna
Opalińska, Marta
Godlewska, Magdalena
Grochowska, Anna
Skalniak, Anna
Hubalewska-Dydejczyk, Alicja
author_facet Gilis-Januszewska, Aleksandra
Bogusławska, Anna
Hasse-Lazar, Kornelia
Jurecka-Lubieniecka, Beata
Jarząb, Barbara
Sowa-Staszczak, Anna
Opalińska, Marta
Godlewska, Magdalena
Grochowska, Anna
Skalniak, Anna
Hubalewska-Dydejczyk, Alicja
author_sort Gilis-Januszewska, Aleksandra
collection PubMed
description Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation.
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spelling pubmed-80671452021-04-25 Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family Gilis-Januszewska, Aleksandra Bogusławska, Anna Hasse-Lazar, Kornelia Jurecka-Lubieniecka, Beata Jarząb, Barbara Sowa-Staszczak, Anna Opalińska, Marta Godlewska, Magdalena Grochowska, Anna Skalniak, Anna Hubalewska-Dydejczyk, Alicja Genes (Basel) Article Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation. MDPI 2021-03-31 /pmc/articles/PMC8067145/ /pubmed/33807230 http://dx.doi.org/10.3390/genes12040512 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
Gilis-Januszewska, Aleksandra
Bogusławska, Anna
Hasse-Lazar, Kornelia
Jurecka-Lubieniecka, Beata
Jarząb, Barbara
Sowa-Staszczak, Anna
Opalińska, Marta
Godlewska, Magdalena
Grochowska, Anna
Skalniak, Anna
Hubalewska-Dydejczyk, Alicja
Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family
title Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family
title_full Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family
title_fullStr Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family
title_full_unstemmed Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family
title_short Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family
title_sort heterogeneity of the clinical presentation of the men1 lrg_509 c.781c>t (p.leu261phe) variant within a three-generation family
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067145/
https://www.ncbi.nlm.nih.gov/pubmed/33807230
http://dx.doi.org/10.3390/genes12040512
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