Novel rare variants in FGFR1 and clinical characteristics analysis in a series of congenital hypogonadotropic hypogonadism patients

Nie, Min; Yu, Bingqing; Chen, Rongrong; Sun, Bang; Mao, Jiangfeng; Wang, Xi; Zhang, Hongbing; Wu, Xueyan

doi:10.1111/cen.14436

Cited by 6 publications

(4 citation statements)

References 39 publications

(91 reference statements)

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“…Three hundred and fifty-seven probands were admitted to Peking Union Medical College Hospital (Beijing, China) between January 2005 and December 2012 and diagnosed as CHH. This study included 327 unrelated CHH Chinese probands: 148 nCHH (141 males; Seven females) and 179 KS (167 males; 12 females), excluding 30 patients diagnosed as carrying FGFR1 variants ( Nie et al, 2021 ). The study was approved by the Ethics Committee for Human Research of Peking Union Medical College Hospital; all patients and guardians of children provided written informed consent.…”

Section: Methodsmentioning

confidence: 99%

Classification of CHD7 Rare Variants in Chinese Congenital Hypogonadotropic Hypogonadism Patients and Analysis of Their Clinical Characteristics

et al. 2022

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Purpose:CHD7 rare variants can cause congenital hypogonadotropic hypogonadism (CHH) and CHARGE syndrome. We aimed to summarize the genotype and phenotype characteristics of CHH patients with CHD7 rare variants.Methods: Rare sequencing variants (RSVs) were detected by Sanger sequencing in a series of 327 CHH patients and were interpreted and grouped according to the American College of Medical Genetics and Genomics (ACMG) guideline. Detailed phenotyping and genotype-phenotype correlation were analyzed.Results: The RSV detection rate was 11.01% (36/327) in the CHH patients. We identified 30 RSVs and 19 of them were novel. Following ACMG criteria, three variants were pathogenic (P), 4 were likely pathogenic (LP), 3 were of uncertain significance with paradoxical evidence (US1), and 20 were of uncertain significance without enough evidence (US2). All patients (4/4, 100%) with P or LP variants manifested extragonadal symptoms.Conclusion: Addition of 19 novel CHD7 variants expanded the spectrum of variants, and pathogenic or likely pathogenic RSVs were more likely to cause syndromic CHH. For CHH patients carrying CHD7 RSVs, detailed genotyping and phenotyping can facilitate clinical diagnosis and therapy.

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Section: Methodsmentioning

confidence: 99%

Classification of CHD7 Rare Variants in Chinese Congenital Hypogonadotropic Hypogonadism Patients and Analysis of Their Clinical Characteristics

et al. 2022

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“…Diagnosis is made by an experienced doctor according to examination results. The diagnostic criteria of KS included the following: (a) patients with absent/incomplete puberty by the age of 18; (b) serum T ≤100 ng/dl with low or normal serum gonadotropin levels; (c) normal hypothalamic–pituitary region magnetic resonance imaging (MRI); (d) normal pituitary–adrenal/pituitary–thyroid/pituitary–IGF-1 axis function; and (e) anosmia or hyposmia ( 6 ). An age-matched control group (healthy volunteers) with normal semen parameters was recruited from PUMCH.…”

Section: Methodsmentioning

confidence: 99%

“…KS has genetic heterogeneity, including three methods of inheritance: autosomal recessive inheritance, autosomal dominant inheritance, and X-linked recessive inheritance (2,3). Currently, it is challenging for doctors to match genetic mutations to phenotypes, leading to the difficult diagnosis of KS (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Seminal Plasma Lipidomics Profiling to Identify Signatures of Kallmann Syndrome

Wang

et al. 2021

Front. Endocrinol.

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BackgroundKallmann syndrome (KS) is a rare developmental disorder. Our previous metabolomics work showed substantial changes in linoleic acid and glycerophospholipid metabolism in KS. Here, we performed targeted lipidomics to further identify the differential lipid species in KS.MethodsTwenty-one patients with KS (treatment group) and twenty-two age-matched healthy controls (HC, control group) were enrolled. Seminal plasma samples and medical records were collected. Targeted lipidomics analysis of these samples was performed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS).ResultsLipidomics profiling of patients with KS and the HCs showed clear separation in the orthogonal projections to latent structures-discriminant analysis (OPLS-DA). There were many differential lipids identified, with the main differential lipid species being triacylglycerols (TAGs), phosphatidylcholines (PCs) and phosphatidylethanolamine (PE).ConclusionsThe lipidomics profile of patients with KS changed. It was also determined that TAGs, PCs and PE are promising biomarkers for KS diagnosis. To our knowledge, this is the first report to analyze lipidomics in men with Kallmann syndrome.

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“…IHH has a high degree of genetic heterogeneity. Variants were described in more than 50 genes [1, 3, 9, 10]. Unbiased genetic methodologies were used to discover several genes.…”

Section: Introductionmentioning

confidence: 99%

SLIT2 Rare Sequencing Variants Identified in Idiopathic Hypogonadotropic Hypogonadism

Fang

Wang

et al. 2022

Horm Res Paediatr

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Introduction: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare reproductive disorder resulting from gonadotropin-releasing hormone (GnRH) deficiency. However, in only approximately half of patients with IHH is it possible to identify a likely molecular diagnosis. Mice lacking Slit2 have a reduced number or altered patterning of GnRH neurons in the brain. In order to assess the contribution of SLIT2 to IHH, we carried out a candidate gene burden test analysis. Methods: A total of 196 IHH probands and 2362 ethic matched controls were recruited for this study. The IHH probands and controls were subjected to whole exome sequencing. In the IHH patients with SLIT2 variants and their available family members, detailed phenotyping and segregation analysis were performed. Results: Nine heterozygous SLIT2 rare sequencing variants (RSVs) were identified in 13 probands, with a prevalence of 6.6%. Furthermore, we identified an increased mutational burden for SLIT2 in this cohort (odds ratio = 2.2, p = 0.021). The segregation analysis of available IHH families revealed that the majority of SLIT2 RSVs were inherited from unaffected or partially affected parents. Conclusion: Our study suggests SLIT2 as a new IHH-associated gene and expands the clinical and genetic spectrum of IHH. Furthermore, SLIT2 alone does not appear to be sufficient to cause the disorder, and it may interact with other IHH-associated genes to induce a clinical phenotype.

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Novel rare variants in FGFR1 and clinical characteristics analysis in a series of congenital hypogonadotropic hypogonadism patients

Cited by 6 publications

References 39 publications

Classification of CHD7 Rare Variants in Chinese Congenital Hypogonadotropic Hypogonadism Patients and Analysis of Their Clinical Characteristics

Classification of CHD7 Rare Variants in Chinese Congenital Hypogonadotropic Hypogonadism Patients and Analysis of Their Clinical Characteristics

Seminal Plasma Lipidomics Profiling to Identify Signatures of Kallmann Syndrome

<b><i>SLIT2</i></b> Rare Sequencing Variants Identified in Idiopathic Hypogonadotropic Hypogonadism

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