An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1

X-linked congenital adrenal hypoplasia due to NR0B1 mutation is characterized by hypogonadotropic hypogonadism (HH) and infertility. Here, we describe a novel pathogenic frameshift variant in NR0B1 associated with congenital adrenal hypoplasia by whole exome sequencing in an Iranian case with high l...

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Main Authors: Samira Kalayinia, Saeed Talebi, Mohammad Miryounesi, Peymaneh Sarkhail, Nejat Mahdieh
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2021/4367028
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author Samira Kalayinia
Saeed Talebi
Mohammad Miryounesi
Peymaneh Sarkhail
Nejat Mahdieh
author_facet Samira Kalayinia
Saeed Talebi
Mohammad Miryounesi
Peymaneh Sarkhail
Nejat Mahdieh
author_sort Samira Kalayinia
collection DOAJ
description X-linked congenital adrenal hypoplasia due to NR0B1 mutation is characterized by hypogonadotropic hypogonadism (HH) and infertility. Here, we describe a novel pathogenic frameshift variant in NR0B1 associated with congenital adrenal hypoplasia by whole exome sequencing in an Iranian case with high level of testosterone. Clinical evaluations and pedigree drawing were performed. Point mutations, gene conversions, and large deletions of the CYP21A2 gene were checked. WES and segregation analyses were conducted. In silico analysis was also performed for the novel variant. The ACTH, 17-hydroxy progesterone c, and DHEA sulfate values were elevated up to 624.6 pg/mL, 8.6 pmol/L, and 17.8UMOL/L, respectively. No mutation was found in the CYP21A2 gene. WES identified a novel hemizygous frameshift insertion c.218_219insACCA: p.His73GlnfsTer41 variant in the NR0B1 gene with a pathogenic effect according to ACMG criteria. Genetic testing is helpful for differential diagnosis in primary adrenal insufficiency disorders. NR0B1 may be a common cause of congenital adrenal hypoplasia in our population.
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language English
publishDate 2021-01-01
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series International Journal of Endocrinology
spelling doaj-art-2ff8c709590f4e219cb6813edb06ab2a2025-08-20T02:07:56ZengWileyInternational Journal of Endocrinology1687-83452021-01-01202110.1155/2021/4367028An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1Samira Kalayinia0Saeed Talebi1Mohammad Miryounesi2Peymaneh Sarkhail3Nejat Mahdieh4Cardiogenetic Research CenterDepartment of Medical GeneticsDepartment of Medical GeneticsPediatric DepartmentCardiogenetic Research CenterX-linked congenital adrenal hypoplasia due to NR0B1 mutation is characterized by hypogonadotropic hypogonadism (HH) and infertility. Here, we describe a novel pathogenic frameshift variant in NR0B1 associated with congenital adrenal hypoplasia by whole exome sequencing in an Iranian case with high level of testosterone. Clinical evaluations and pedigree drawing were performed. Point mutations, gene conversions, and large deletions of the CYP21A2 gene were checked. WES and segregation analyses were conducted. In silico analysis was also performed for the novel variant. The ACTH, 17-hydroxy progesterone c, and DHEA sulfate values were elevated up to 624.6 pg/mL, 8.6 pmol/L, and 17.8UMOL/L, respectively. No mutation was found in the CYP21A2 gene. WES identified a novel hemizygous frameshift insertion c.218_219insACCA: p.His73GlnfsTer41 variant in the NR0B1 gene with a pathogenic effect according to ACMG criteria. Genetic testing is helpful for differential diagnosis in primary adrenal insufficiency disorders. NR0B1 may be a common cause of congenital adrenal hypoplasia in our population.http://dx.doi.org/10.1155/2021/4367028
spellingShingle Samira Kalayinia
Saeed Talebi
Mohammad Miryounesi
Peymaneh Sarkhail
Nejat Mahdieh
An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1
International Journal of Endocrinology
title An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1
title_full An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1
title_fullStr An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1
title_full_unstemmed An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1
title_short An Iranian Congenital Adrenal Hypoplasia Patient with Elevated Testosterone in Infancy due to a Novel Pathogenic Frameshift Variant in NR0B1
title_sort iranian congenital adrenal hypoplasia patient with elevated testosterone in infancy due to a novel pathogenic frameshift variant in nr0b1
url http://dx.doi.org/10.1155/2021/4367028
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