Clinical, hormonal, and genetic characteristics of 25 Chinese patients with idiopathic hypogonadotropic hypogonadism

Liu, Qingxu; Yin, Xiaoqin; Пин, Ли

doi:10.1186/s12902-022-00940-9

Cited by 7 publications

(6 citation statements)

References 29 publications

(33 reference statements)

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“…Among the 6 variants assessed as pathogenic or possibly pathogenic, 5 were CHD7 genes (83.3%), which was significantly different from many study cohorts. CHD7 accounted for 4% [ 33 ], 8.2% [ 34 ], and 26.7% [ 26 , 27 ] of the detected genes in multiple cohorts. CHD7 is a large nucleoprotein containing two N-terminal chromosomal domains, a central Snf2-like ATPASE and helicase domain, a histone/DNA binding SANT domain, and two C-terminal BRK domains.…”

Section: Resultsmentioning

confidence: 99%

The Clinical and Genetic Characteristics in Children with Idiopathic Hypogonadotropin Hypogonadism

Zhang

Yang

Zou

2022

Journal of Oncology

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Background. Idiopathic hypogonadotropin hypogonadism (IHH) is caused by hypothalamic-pituitary-gonadal axis dysfunction. This is divided into Kallmann syndrome which has an impaired sense of smell and hypogonadotropin hypogonadism with normal olfactory (nIHH sense. Approximately 60% of patients are associated with Kallmann syndrome, whereas there are approximately 40% with hypogonadotropin hypogonadism (nIHH). This disease is associated with various variants in genes along with different phenotypic characteristics, and even those gene variations could also lead to the cancer formation in patients. So, current study has been designed to investigate and to better understand the characteristics of various IHH-associated genes and the correlation between IHH genes and phenotype. Methods. The cohort included 14 children with IHH (6 patients of KS and 8 patients of IHH), including 13 boys and 1 girl. Exclusion criteria are as follows: diagnosis of secondary hypogonadotropin hypogonadism due to tumor, trauma, drugs, or other systemic diseases. Clinical data and genetic results were analyzed. Results. Almost all male patients showed micropenis (12/13, 92.3%), and few of them had cryptorchidism (5/13, 41.7%). A total of 6 genes, CHD7, PROKR2, ANOS1, FGFR1, SEMA3A, and NDNF, were detected. CHD7 was the most common (11/17, 64.7%), and the main mutation type was missense mutation (14/16, 87.5%). Six reported variants and 10 new variants (5 genes, including entire ANSO1 duplicates) were found. Neonatal variation was detected in 3 patients with IHH. Eight patients inherited the variation from their father, while five patients inherited it from their mother. One patient had both FGFR1 and SEMA3A gene variants, while the other had two different CHD7 gene variants and entire ANSO1 repeats. According to ACMG criteria, 4 variants were pathogenic (P), 2 were possibly pathogenic (LP), and 8 had uncertain significance (US). In patients with P or LP (5/6, 83.3%), we found that extragonadal symptoms were more common. Conclusions. It was concluded that variations in the studied genes could lead to the IHH. Ten new variants have been reported which may lead to different symptoms of IHH. For CHD7 variants, the rare sequencing variants (RSVs) of P or LP showed commonly associated with CHARGE syndrome. Findings of the current study may help for the better diagnosis and treatment of IHH.

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Section: Resultsmentioning

confidence: 99%

The Clinical and Genetic Characteristics in Children with Idiopathic Hypogonadotropin Hypogonadism

Zhang

Yang

Zou

2022

Journal of Oncology

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“…In our report, proband 2 presented with azoospermia mainly due to secondary gonadal dysfunction. The proband has been initially misdiagnosed as IHH, a rare type of congenital disease characterized with dysfunction in the secretion of hypothalamic GnRH and reduced serum levels of sex steroids ( 22 ). In fact, the lower normal range of testosterone with suppressed gonadotropins is also the typical profile of secondary hypogonadotropic hypogonadism ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Genotype-phenotype correlation in patients with 21-hydroxylase deficiency

et al. 2023

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Introduction21-hydroxylase deficiency (21OHD) is the most common cause of congenital adrenal hyperplasia (CAH). However, patients with 21OHD manifest various phenotypes due to a wide-spectrum residual enzyme activity of different CYP21A2 mutations.MethodsA total of 15 individuals from three unrelated families were included in this study. Target Capture-Based Deep Sequencing and Restriction Fragment Length Polymorphism was conducted on peripheral blood DNA of the three probands to identify potential mutations/deletions in CYP21A2; Sanger sequencing was conducted with the DNA from the family members of the probands.ResultsDramatically different phenotypes were seen in the three probands of CAH with different compound heterozygous mutations in CYP21A2. Proband 1 manifested simple virilizing with mutations of 30-kb deletion/c.[188A>T;518T>A], the latter is a novel double mutants classified as SV associated mutation. Although both probands carry the same compound mutations [293-13C>G]:[518T>A], gonadal dysfunction and giant bilateral adrenal myelolipoma were diagnosed for proband 2 and proband 3, respectively.ConclusionBoth gender and mutations contribute to the phenotypes, and patients with the same compound mutations and gender could present with different phenotypes. Genetic analysis could help the etiologic diagnosis, especially for atypical 21OHD patients.

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“…Some variants have a clear regional predominance. The p.W178S variant seems to be most prevalent in continental Asia (mainly in China, although it has also been reported in South Korea and Japan) (10,30,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). Nevertheless the variant has also been described in the USA and France, in patients of undisclosed ethnicity (9,29).…”

Section: Prokr2 Variants Around the Worldmentioning

confidence: 99%

“…Other missense variants unique to Asia are p.G57C, p.A103V and p.Y113H ( 23 , 29 – 31 , 38 , 41 – 44 , 46 – 51 ). The variants p.G57C, p.A103V were found in two and five patients with KS/HH respectively and both are classified as variants of uncertain significance (VUS) with a frequency of 1/1000 in this population.…”

Section: Prokr2 Variants Around the Worldmentioning

confidence: 99%

Phenotypic and genotypic landscape of PROKR2 in neuroendocrine disorders

Martinez-Mayer

Pérez-Millán

2023

Front. Endocrinol.

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Prokineticin receptor 2 (PROKR2) encodes for a G-protein-coupled receptor that can bind PROK1 and PROK2. Mice lacking Prokr2 have been shown to present abnormal olfactory bulb formation as well as defects in GnRH neuron migration. Patients carrying mutations in PROKR2 typically present hypogonadotropic hypogonadism, anosmia/hyposmia or Kallmann Syndrome. More recently variants in PROKR2 have been linked to several other endocrine disorders. In particular, several patients with pituitary disorders have been reported, ranging from mild phenotypes, such as isolated growth hormone deficiency, to more severe ones, such as septo-optic dysplasia. Here we summarize the changing landscape of PROKR2-related disease, the variants reported to date, and discuss their origin, classification and functional assessment.

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Clinical, hormonal, and genetic characteristics of 25 Chinese patients with idiopathic hypogonadotropic hypogonadism

Cited by 7 publications

References 29 publications

The Clinical and Genetic Characteristics in Children with Idiopathic Hypogonadotropin Hypogonadism

The Clinical and Genetic Characteristics in Children with Idiopathic Hypogonadotropin Hypogonadism

Genotype-phenotype correlation in patients with 21-hydroxylase deficiency

Phenotypic and genotypic landscape of PROKR2 in neuroendocrine disorders

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