Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblings
Hypogonadotropic hypogonadism is characterised by insufficient secretion of pituitary gonadotropins resulting in delayed puberty, anovulation and azoospermia. When hypogonadotropic hypogonadism occurs in the absence of structural or functional lesions of the hypothalamic or pituitary gland, the hypo...
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Bioscientifica
2020-03-01
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Series: | Endocrinology, Diabetes & Metabolism Case Reports |
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doaj-2583c6ed836341359727ba15c8d423c22020-11-25T02:10:36ZengBioscientificaEndocrinology, Diabetes & Metabolism Case Reports2052-05732052-05732020-03-01111510.1530/EDM-19-0145Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblingsSatyanarayana V Sagi0Hareesh Joshi1Emily Whiles2Mondy Hikmat3Vijith R Puthi4Jane MacDougall5Sarah L Spiden6Gavin Fuller7Soo-Mi Park8Samson O Oyibo9Department of Diabetes and Endocrinology, Peterborough City Hospital, Peterborough, UKDepartment of Diabetes and Endocrinology, Peterborough City Hospital, Peterborough, UKDepartment of Diabetes and Endocrinology, Peterborough City Hospital, Peterborough, UKDepartment of Diabetes and Endocrinology, Peterborough City Hospital, Peterborough, UKDepartment of Paediatrics, Peterborough City Hospital, Peterborough, UKDepartment of Reproductive Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UKEast Midlands and East of England NHS Genomic Laboratory Hub, Cambridge University Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UKEast Midlands and East of England NHS Genomic Laboratory Hub, Cambridge University Hospital NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UKDepartment of Clinical Genetics Service, Cambridge University Hospital NHS Foundation Trust, Cambridge, UKDepartment of Diabetes and Endocrinology, Peterborough City Hospital, Peterborough, UKHypogonadotropic hypogonadism is characterised by insufficient secretion of pituitary gonadotropins resulting in delayed puberty, anovulation and azoospermia. When hypogonadotropic hypogonadism occurs in the absence of structural or functional lesions of the hypothalamic or pituitary gland, the hypogonadism is defined as idiopathic hypogonadotropic hypogonadism (IHH). This is a rare genetic disorder caused by a defect in the secretion of gonadotropin releasing hormone (GNRH) by the hypothalamus or a defect in the action of GNRH on the pituitary gland. Up to 50% of IHH cases have identifiable pathogenic variants in the currently known genes. Pathogenic variants in the GNRHR gene encoding the GNRH receptor are a relatively common cause of normosmic IHH, but reports of pathogenic variants in GNRH1 encoding GNRH are exceedingly rare. We present a case of two siblings born to consanguineous parents who were found to have normosmic idiopathic hypogonadotropic hypogonadism due to homozygosity of a novel loss-of function variant in GNRH1. Case 1 is a male who presented at the age of 17 years with delayed puberty and under-virilised genitalia. Case 2 is a female who presented at the age of 16 years with delayed puberty and primary amenorrhea.https://edm.bioscientifica.com/view/journals/edm/2020/1/EDM19-0145.xml |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Satyanarayana V Sagi Hareesh Joshi Emily Whiles Mondy Hikmat Vijith R Puthi Jane MacDougall Sarah L Spiden Gavin Fuller Soo-Mi Park Samson O Oyibo |
spellingShingle |
Satyanarayana V Sagi Hareesh Joshi Emily Whiles Mondy Hikmat Vijith R Puthi Jane MacDougall Sarah L Spiden Gavin Fuller Soo-Mi Park Samson O Oyibo Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblings Endocrinology, Diabetes & Metabolism Case Reports |
author_facet |
Satyanarayana V Sagi Hareesh Joshi Emily Whiles Mondy Hikmat Vijith R Puthi Jane MacDougall Sarah L Spiden Gavin Fuller Soo-Mi Park Samson O Oyibo |
author_sort |
Satyanarayana V Sagi |
title |
Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblings |
title_short |
Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblings |
title_full |
Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblings |
title_fullStr |
Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblings |
title_full_unstemmed |
Normosmic idiopathic hypogonadotropic hypogonadism due to a novel GNRH1 variant in two siblings |
title_sort |
normosmic idiopathic hypogonadotropic hypogonadism due to a novel gnrh1 variant in two siblings |
publisher |
Bioscientifica |
series |
Endocrinology, Diabetes & Metabolism Case Reports |
issn |
2052-0573 2052-0573 |
publishDate |
2020-03-01 |
description |
Hypogonadotropic hypogonadism is characterised by insufficient secretion of pituitary gonadotropins resulting in delayed puberty, anovulation and azoospermia. When hypogonadotropic hypogonadism occurs in the absence of structural or functional lesions of the hypothalamic or pituitary gland, the hypogonadism is defined as idiopathic hypogonadotropic hypogonadism (IHH). This is a rare genetic disorder caused by a defect in the secretion of gonadotropin releasing hormone (GNRH) by the hypothalamus or a defect in the action of GNRH on the pituitary gland. Up to 50% of IHH cases have identifiable pathogenic variants in the currently known genes. Pathogenic variants in the GNRHR gene encoding the GNRH receptor are a relatively common cause of normosmic IHH, but reports of pathogenic variants in GNRH1 encoding GNRH are exceedingly rare. We present a case of two siblings born to consanguineous parents who were found to have normosmic idiopathic hypogonadotropic hypogonadism due to homozygosity of a novel loss-of function variant in GNRH1. Case 1 is a male who presented at the age of 17 years with delayed puberty and under-virilised genitalia. Case 2 is a female who presented at the age of 16 years with delayed puberty and primary amenorrhea. |
url |
https://edm.bioscientifica.com/view/journals/edm/2020/1/EDM19-0145.xml |
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