A Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature

Primary ovarian insufficiency (POI) refers to an etiologically heterogeneous disorder characterized by hypergonadotropic hypogonadism that represents a major cause of infertility in women under 40 years of age. Most cases are apparently sporadic, but about 10–15% have an affected first-degree relati...

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Autores principales:	Simona Mellone, Marco Zavattaro, Denise Vurchio, Sara Ronzani, Marina Caputo, Ilaria Leone, Flavia Prodam, Mara Giordano
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>STAG3</i> primary ovarian insufficiency exome sequencing LCSH Genetics QH426-470
Acceso en línea:	https://doaj.org/article/c57a9338742d4f5cafea1e3d32d60a7a
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spelling	oai:doaj.org-article:c57a9338742d4f5cafea1e3d32d60a7a2021-11-25T17:41:06ZA Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature10.3390/genes121117092073-4425https://doaj.org/article/c57a9338742d4f5cafea1e3d32d60a7a2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1709https://doaj.org/toc/2073-4425Primary ovarian insufficiency (POI) refers to an etiologically heterogeneous disorder characterized by hypergonadotropic hypogonadism that represents a major cause of infertility in women under 40 years of age. Most cases are apparently sporadic, but about 10–15% have an affected first-degree relative, indicating a genetic etiology. Pathogenic variations in genes involved in development, meiosis and hormonal signaling have been detected in the hereditary form of the disorder. However, most cases of POI remain unsolved even after exhaustive investigation. A 19-year-old Senegalese female affected by non-syndromic POI presented with primary amenorrhoea and answered well to the hormonal induction of puberty. In order to investigate the presence of a genetic defect, aCGH-SNP analysis was performed. A 13.5 Mb long contiguous stretch of homozygosity (LCSH) was identified on chromosome 7q21.13-q22.1 where the exome sequencing revealed a novel homozygous 4-bp deletion (c.3381_3384delAGAA) in <i>STAG3</i>. Pathogenic variants in this gene, encoding for a meiosis-specific protein, have been previously reported as the cause of POI in only eight families and recently as the cause of infertility in a male. The here-identified mutation leads to the truncation of the last 55 amino acids, confirming the important role in meiosis of the <i>STAG3</i> C-terminal domain.Simona MelloneMarco ZavattaroDenise VurchioSara RonzaniMarina CaputoIlaria LeoneFlavia ProdamMara GiordanoMDPI AGarticle<i>STAG3</i>primary ovarian insufficiencyexome sequencingLCSHGeneticsQH426-470ENGenes, Vol 12, Iss 1709, p 1709 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>STAG3</i> primary ovarian insufficiency exome sequencing LCSH Genetics QH426-470
spellingShingle	<i>STAG3</i> primary ovarian insufficiency exome sequencing LCSH Genetics QH426-470 Simona Mellone Marco Zavattaro Denise Vurchio Sara Ronzani Marina Caputo Ilaria Leone Flavia Prodam Mara Giordano A Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature
description	Primary ovarian insufficiency (POI) refers to an etiologically heterogeneous disorder characterized by hypergonadotropic hypogonadism that represents a major cause of infertility in women under 40 years of age. Most cases are apparently sporadic, but about 10–15% have an affected first-degree relative, indicating a genetic etiology. Pathogenic variations in genes involved in development, meiosis and hormonal signaling have been detected in the hereditary form of the disorder. However, most cases of POI remain unsolved even after exhaustive investigation. A 19-year-old Senegalese female affected by non-syndromic POI presented with primary amenorrhoea and answered well to the hormonal induction of puberty. In order to investigate the presence of a genetic defect, aCGH-SNP analysis was performed. A 13.5 Mb long contiguous stretch of homozygosity (LCSH) was identified on chromosome 7q21.13-q22.1 where the exome sequencing revealed a novel homozygous 4-bp deletion (c.3381_3384delAGAA) in <i>STAG3</i>. Pathogenic variants in this gene, encoding for a meiosis-specific protein, have been previously reported as the cause of POI in only eight families and recently as the cause of infertility in a male. The here-identified mutation leads to the truncation of the last 55 amino acids, confirming the important role in meiosis of the <i>STAG3</i> C-terminal domain.
format	article
author	Simona Mellone Marco Zavattaro Denise Vurchio Sara Ronzani Marina Caputo Ilaria Leone Flavia Prodam Mara Giordano
author_facet	Simona Mellone Marco Zavattaro Denise Vurchio Sara Ronzani Marina Caputo Ilaria Leone Flavia Prodam Mara Giordano
author_sort	Simona Mellone
title	A Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature
title_short	A Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature
title_full	A Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature
title_fullStr	A Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature
title_full_unstemmed	A Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature
title_sort	long contiguous stretch of homozygosity disclosed a novel <i>stag3</i> biallelic pathogenic variant causing primary ovarian insufficiency: a case report and review of the literature
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c57a9338742d4f5cafea1e3d32d60a7a
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A Long Contiguous Stretch of Homozygosity Disclosed a Novel <i>STAG3</i> Biallelic Pathogenic Variant Causing Primary Ovarian Insufficiency: A Case Report and Review of the Literature

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