115 results match your criteria Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism

Clinical and molecular features of idiopathic hypogonadotropic hypogonadism in Taiwan: A single center experience.

J Formos Med Assoc 2021 Mar 25. Epub 2021 Mar 25.

Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Background: Idiopathic (isolated) hypogonadotropic hypogonadism (IHH) is a rare disease that can be classified as Kallmann syndrome (KS) or normosmic IHH (nIHH). This study investigated the phenotype and genotype of IHH in Taiwanese patients.

Methods: Twenty-six unrelated IHH patients were included in this study and their clinical, hormonal, and radiological findings were analyzed retrospectively. Read More

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Kallmann Syndrome Due to Heterozygous Mutation in Coexisting With Waardenburg Syndrome Type II: Case Report and Review of Literature.

Front Endocrinol (Lausanne) 2020 1;11:592831. Epub 2021 Feb 1.

Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital, China Medical University, Shenyang, China.

Introduction: Kallmann syndrome (KS) is idiopathic hypogonadotropic hypogonadism with olfactory loss or decline. Waardenburg syndrome type II (WS2) is a clinically and genetically heterogeneous disease, characterized by congenital sensorineural deafness and abnormal pigmentation of the iris, hair, and skin. Recently, mutations in the well-known WS pathogenic gene have been found in some KS patients with deafness, but whether is a co-pathogenic gene of KS and WS remains uncertain. Read More

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February 2021

Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism.

Genet Med 2021 Jan 25. Epub 2021 Jan 25.

Department of Pediatrics, Division of Pediatric Endocrinology, University of Mississippi Medical Center, Jackson, MS, USA.

Purpose: Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. Read More

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January 2021

Phenotypic continuum between Waardenburg syndrome and idiopathic hypogonadotropic hypogonadism in humans with SOX10 variants.

Genet Med 2021 Apr 13;23(4):629-636. Epub 2021 Jan 13.

Harvard Reproductive Sciences Center, The Reproductive Endocrine Unit and The Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Purpose: SOX10 variants previously implicated in Waardenburg syndrome (WS) have now been linked to Kallmann syndrome (KS), the anosmic form of idiopathic hypogonadotropic hypogonadism (IHH). We investigated whether SOX10-associated WS and IHH represent elements of a phenotypic continuum within a unifying disorder or if they represent phenotypically distinct allelic disorders.

Methods: Exome sequencing from 1,309 IHH subjects (KS: 632; normosmic idiopathic hypogonadotropic hypogonadism [nIIHH]: 677) were reviewed for SOX10 rare sequence variants (RSVs). Read More

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GnRH in the treatment of Hypogonadotropic hypogonadism.

Curr Pharm Des 2020 Nov 24. Epub 2020 Nov 24.

Department of Emergency and Organ Transplantation - Urology, Andrology and Kidney Transplantation Unit - University of Bari. Italy.

Gonadotropin Releasing Hormone (GnRH) is at the centre of the scientific debate for the treatment of hypogonadotropic hypogonadism. Sexual maturation and reproductive function depend on the pulsatile secretion of GnRH are mainly congenital and may or may not be associated with other genetic anomalies or syndromes. Clinical manifestations include a wide range of metabolic, endocrine and psychologic dysfunctions. Read More

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November 2020

Dizygotic twin sisters with normosmic idiopathic hypogonadotropic hypogonadism caused by an FGFR1 gene variant.

Ann Pediatr Endocrinol Metab 2020 Sep 29;25(3):192-197. Epub 2020 Jul 29.

Department of Pediatrics, Inje University Ilsan Paik Hospital, Goyang, Korea.

Isolated hypogonadotropic hypogonadism (IHH) is a rare genetic disorder that is clinically and genetically heterogeneous. It is characterized by absent or incomplete pubertal development owing to an isolated defect in the production, secretion, or action of gonadotropin-releasing hormone. The incidence of IHH is estimated at 1:30,000 in males and 1:125,000 in females. Read More

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September 2020

Spermatogenesis of Male Patients with Congenital Hypogonadotropic Hypogonadism Receiving Pulsatile Gonadotropin-Releasing Hormone Therapy Gonadotropin Therapy: A Systematic Review and Meta-Analysis.

World J Mens Health 2020 Jul 14. Epub 2020 Jul 14.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Purpose: Pulsatile gonadotropin-releasing hormone (GnRH) therapy and gonadotropin therapy (GT) were widely used for male patients with congenital hypogonadotropic hypogonadism (CHH), but their efficacy was not well compared before. We conducted this meta-analysis to compare the efficacy of restoring fertility using these two therapies.

Materials And Methods: PubMed, Web of Science, and Scopus were systematically searched for comparative studies evaluating the efficiency of GnRH therapy and GT for male patients with CHH. Read More

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The wonderful and masterful G protein-coupled receptor (GPCR): A focus on signaling mechanisms and the neuroendocrine control of fertility.

Andy V Babwah

Mol Cell Endocrinol 2020 09 20;515:110886. Epub 2020 Jun 20.

Department of Pediatrics, Laboratory of Human Growth and Reproductive Development, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States; Child Health Institute of New Jersey, New Brunswick, NJ, United States. Electronic address:

Human GnRH deficiency, both clinically and genetically, is a heterogeneous disorder comprising of congenital GnRH deficiency with anosmia (Kallmann syndrome), or with normal olfaction [normosmic idiopathic hypogonadotropic hypogonadism (IHH)], and adult-onset hypogonadotropic hypogonadism. Our understanding of the neural mechanisms underlying GnRH secretion and GnRH signaling continues to increase at a rapid rate and strikingly, the heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) continue to emerge as essential players in these processes. GPCRs were once viewed as binary on-off switches, where in the "on" state they are bound to their Gα protein, but now we understand that view is overly simplistic and does not adequately characterize GPCRs. Read More

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September 2020

Functional Characteristics of Novel FGFR1 Mutations in Patients with Isolated Gonadotropin-Releasing Hormone Deficiency.

Exp Clin Endocrinol Diabetes 2020 Jun 2. Epub 2020 Jun 2.

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Background: Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) has a wide phenotypic spectrum including Kallmann syndrome (KS) and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). mutations have been identified in 3-10% of patients with KS or nIHH. This study was performed to investigate clinical phenotypes and functional characteristics of mutations in patients with IGD. Read More

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Parallel Multi-Gene Panel Testing for Diagnosis of Idiopathic Hypogonadotropic Hypogonadism/Kallmann Syndrome.

Case Rep Genet 2019 27;2019:4218514. Epub 2019 Oct 27.

Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, 632 004 Vellore, India.

Kallmann syndrome (KS)/Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by hypogonadotropic hypogonadism and anosmia or hyposmia due to the abnormal migration of olfactory and gonadotropin releasing hormone producing neurons. Multiple genes have been implicated in KS/IHH. Sequential testing of these genes utilising Sanger sequencing is time consuming and not cost effective. Read More

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October 2019

Phenotypic Spectrum of Idiopathic Hypogonadotropic Hypogonadism Patients With CHD7 Variants From a Large Chinese Cohort.

J Clin Endocrinol Metab 2020 05;105(5)

School of Life Sciences, Central South University, Changsha, Hunan, China.

Purpose: Idiopathic hypogonadotropic hypogonadism (IHH) and CHARGE (C, coloboma; H, heart abnormalities; A, choanal atresia, R, retardation of growth and/or development; G, gonadal defects; E, ear deformities and deafness) syndrome are 2 distinct developmental disorders sharing features of hypogonadism and/or impaired olfaction. CHD7 variants contribute to >60% CHARGE syndrome and ~10% IHH patients. A variety of extended CHARGE-like features are frequently reported in CHARGE patients harboring CHD7 variants. Read More

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A novel splice site variant in ANOS1 gene leads to Kallmann syndrome in three siblings.

Gene 2020 Feb 26;726:144177. Epub 2019 Oct 26.

Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetic disease caused by low doses of hypothalamic gonadotropin-releasing hormone (GnRH), leading to absence or delayed sexual development. Kallmann syndrome (KS) is characterized by IHH with anosmia or hyposmia. Here, we identified a novel splice site variant (c. Read More

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February 2020

Correlation of Olfactory Phenotype by Indian Smell Identification Test and Quantitative MRI of Olfactory Apparatus in Idiopathic Hypogonadotropic Hypogonadism.

Indian J Endocrinol Metab 2019 May-Jun;23(3):367-372

Department of Endocrinology, SMS Medical College, Jaipur, Rajasthan, India.

Objectives: Idiopathic hypogonadotropic hypogonadism (IHH) can be associated with anosmia/hyposmia. The objective of this study is to evaluate olfaction by Indian smell identification test (INSIT) and measure olfactory bulbs (OBs) and sulci using dedicated magnetic resonance imaging (MRI) in patients with IHH and correlate MRI findings with INSIT.

Methods: Forty patients with IHH underwent (a) brief smell identification test (INSIT) and (b) MRI of the olfactory apparatus. Read More

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October 2019

Thyroid function in Klinefelter syndrome: a multicentre study from KING group.

J Endocrinol Invest 2019 Oct 25;42(10):1199-1204. Epub 2019 Mar 25.

Department of Advanced Medical And Surgical Sciences, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.

Purpose: The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients. Read More

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October 2019

Prevalence and associated phenotypes of PLXNA1 variants in normosmic and anosmic idiopathic hypogonadotropic hypogonadism.

Clin Genet 2019 02 26;95(2):320-324. Epub 2018 Dec 26.

Division of Pediatric Endocrinology, Cukurova University, Faculty of Medicine, Adana, Turkey.

Idiopathic hypogonadotropic hypogonadism (IHH) can be divided into two major forms, normosmic IHH and Kallmann syndrome (KS). Genetic mutations are responsible for the majority of IHH. PLXNA1 has recently been implicated in the GnRH neuron migration and the etiology of KS. Read More

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February 2019

Targeted Gene Panel Sequencing for Molecular Diagnosis of Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism.

Exp Clin Endocrinol Diabetes 2019 Sep 14;127(8):538-544. Epub 2018 Sep 14.

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Background: Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is classified either as Kallmann syndrome (KS) with anosmia or normosmic idiopathic hypogonadotropic hypogonadism (nIHH) and caused by mutations in more than 30 different genes. Recent advances in next-generation sequencing technologies have revolutionized the identification of causative genes by using massively parallel sequencing of multiple samples. This study was performed to establish the genetic etiology of IGD using a targeted gene panel sequencing of 69 known human IGD genes. Read More

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September 2019

Update on the Genetics of Idiopathic Hypogonadotropic Hypogonadism.

J Clin Res Pediatr Endocrinol 2017 Dec 27;9(Suppl 2):113-122. Epub 2017 Dec 27.

University of Mississippi Medical Center, Department of Pediatrics, Division of Pediatric Endocrinology and Department of Neurobiology and Anatomical Sciences, Jackson, Mississippi, USA.

Traditionally, idiopathic hypogonadotropic hypogonadism (IHH) is divided into two major categories: Kallmann syndrome (KS) and normosmic IHH (nIHH). To date, inactivating variants in more than 50 genes have been reported to cause IHH. These mutations are estimated to account for up to 50% of all apparently hereditary cases. Read More

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December 2017

Reproductive endocrine phenotypes relating to CHD7 mutations in humans.

Am J Med Genet C Semin Med Genet 2017 12 20;175(4):507-515. Epub 2017 Nov 20.

Harvard Reproductive Endocrine Sciences Center of Excellence in Translation Research & Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Mutations in the gene CHD7 cause CHARGE syndrome, a rare multi-organ syndromic disorder. Gonadal defects are common in individuals with CHARGE syndrome (seen in ∼60-80% of cases) and represent the letter "G" in the CHARGE syndrome acronym. The gonadal defect in CHARGE syndrome results from congenital deficiency of the hypothalamic hormone Gonadotropin-releasing hormone (GnRH), which manifests clinically as pubertal failure and infertility, and biochemically as hypogonadotropic hypogonadism (low sex steroid hormone levels with inappropriately normal or low gonadotropin levels). Read More

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December 2017

Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism.

Metabolism 2018 09 3;86:124-134. Epub 2017 Nov 3.

University of Patras Medical School, University Hospital, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Rion, Patras, Achaia, Greece.

Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency (IGD) IGD is a genetically and clinically heterogeneous disorder. Mutations in many different genes are able to explain ~40% of the causes of IGD, with the rest of cases remaining genetically uncharacterized. While most mutations are inherited in X-linked, autosomal dominant, or autosomal recessive pattern, several IGD genes are shown to interact with each other in an oligogenic manner. Read More

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September 2018

Clinical characteristics of 138 Chinese female patients with idiopathic hypogonadotropic hypogonadism.

Endocr Connect 2017 Nov 10;6(8):800-810. Epub 2017 Oct 10.

Department of Obstetrics and GynecologyPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People's Republic of China.

Objective: To evaluate the clinical features of Chinese women with idiopathic hypogonadotropic hypogonadism (IHH).

Methods: We retrospectively reviewed the clinical characteristics, laboratory and imaging findings, therapeutic management and fertility outcomes of 138 women with IHH. All patients had been treated and followed up at an academic medical centre during 1990-2016. Read More

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November 2017

Retro- and orthonasal olfactory function in relation to olfactory bulb volume in patients with hypogonadotrophic hypogonadism.

Braz J Otorhinolaryngol 2018 Sep - Oct;84(5):630-637. Epub 2017 Aug 24.

University of Dresden Medical School, Smell & Taste Interdisciplina Center, Department of Otorhinolaryngology, Dresden, Germany.

Introduction: Idiopathic hypogonadotrophic hypogonadism with an olfactory deficit is defined as Kallmann syndrome and is distinct from normosmic idiopathic hypogonadotrophic hypogonadism.

Objective: Because olfactory perception not only consists of orthonasally gained impressions but also involves retronasal olfactory function, in this study we decided to comprehensively evaluate both retronasal and orthonasal olfaction in patients with idiopathic hypogonadotrophic hypogonadism.

Methods: This case-control study included 31 controls and 45 idiopathic hypogonadotrophic hypogonadism patients. Read More

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February 2019

CCDC141 Mutations in Idiopathic Hypogonadotropic Hypogonadism.

J Clin Endocrinol Metab 2017 06;102(6):1816-1825

Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, 01330 Adana, Turkey.

Context: Gonadotropin-releasing hormone neurons originate outside the central nervous system in the olfactory placode and migrate into the central nervous system, becoming integral components of the hypothalamic-pituitary-gonadal axis. Failure of this migration can lead to idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS). We have previously shown that CCDC141 knockdown leads to impaired migration of GnRH neurons but not of olfactory receptor neurons. Read More

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The mystery of puberty initiation: genetics and epigenetics of idiopathic central precocious puberty (ICPP).

J Endocrinol Invest 2017 Aug 1;40(8):789-802. Epub 2017 Mar 1.

Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Faculty of Medicine, National and Kapodistrian University of Athens, Medical School, "Aghia Sofia" Children's Hospital, Athens, Greece.

Puberty is a major developmental stage. Damaging mutations, considered as "mistakes of nature", have contributed to the unraveling of the networks implicated in the normal initiation of puberty. Genes involved in the abnormal hypothalamic-pituitary-gonadal (HPG) axis development, in the normosmic idiopathic hypogonadotropic hypogonadism (nIHH), in the X-linked or autosomal forms of Kallmann syndrome and in precocious puberty have been identified (GNRH1, GNRHR, KISS1, GPR54, FGFR1, FGF8, PROK2, PROKR2, TAC3, TACR3, KAL1, PROK2, PROKR2, CHD7, LEP, LEPR, PC1, DAX1, SF-1, HESX-1, LHX3, PROP-1). Read More

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Hypogonadotropic Hypogonadism due to Novel FGFR1 Mutations.

J Clin Res Pediatr Endocrinol 2017 Jun 23;9(2):95-100. Epub 2016 Dec 23.

Çukurova University Faculty of Medicine, Division of Pediatric Endocrinology, Adana, Turkey, E-mail:

Objective: The underlying genetic etiology of hypogonadotropic hypogonadism (HH) is heterogeneous. Fibroblast growth factor signaling is pivotal in the ontogeny of gonadotropin-releasing hormone neurons. Loss-of-function mutations in FGFR1 gene cause variable HH phenotypes encompassing pubertal delay to idiopathic HH (IHH) or Kallmann syndrome (KS). Read More

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Sexuality and quality of life in congenital hypogonadisms.

Gynecol Endocrinol 2016 Dec 4;32(12):947-950. Epub 2016 Nov 4.

b Clinic Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic-Institut, d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona , Barcelona , Spain.

Turner syndrome and idiopathic congenital hypogonadism including Kallmann syndrome are conditions associated to a large number of widely known comorbidities that need a medical support forever. One of the characteristics shared by both conditions is the lack of sexual development that influencing the sexuality functioning and quality of life of the affected women. Few studies have been conducted to assess these topics, but they need to be considered in the treatment to all women with hypogonadism. Read More

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December 2016

A Jacob/Nsmf Gene Knockout Results in Hippocampal Dysplasia and Impaired BDNF Signaling in Dendritogenesis.

PLoS Genet 2016 Mar 15;12(3):e1005907. Epub 2016 Mar 15.

Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.

Jacob, the protein encoded by the Nsmf gene, is involved in synapto-nuclear signaling and docks an N-Methyl-D-Aspartate receptor (NMDAR)-derived signalosome to nuclear target sites like the transcription factor cAMP-response-element-binding protein (CREB). Several reports indicate that mutations in NSMF are related to Kallmann syndrome (KS), a neurodevelopmental disorder characterized by idiopathic hypogonadotropic hypogonadism (IHH) associated with anosmia or hyposmia. It has also been reported that a protein knockdown results in migration deficits of Gonadotropin-releasing hormone (GnRH) positive neurons from the olfactory bulb to the hypothalamus during early neuronal development. Read More

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Dominant-negative kinase domain mutations in FGFR1 can explain the clinical severity of Hartsfield syndrome.

Hum Mol Genet 2016 05 29;25(10):1912-1922. Epub 2016 Feb 29.

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA,

Mutations in FGFR1 have recently been associated with Hartsfield syndrome, a clinically distinct syndromic form of holoprosencephaly (HPE) with ectrodactly, which frequently includes combinations of craniofacial, limb and brain abnormalities not typical for classical HPE. Unrelated clinical conditions generally without craniofacial or multi-system malformations include Kallmann syndrome and idiopathic hypogonadotropic hypogonadism. FGFR1 is a principal cause for these less severe diseases as well. Read More

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Clinical characteristics and follow-up of 5 young Chinese males with gonadotropin-releasing hormone deficiency caused by mutations in the KAL1 gene.

Meta Gene 2016 Feb 3;7:64-9. Epub 2015 Dec 3.

Department of Endocrinology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) pertains to a group of genetic disorders consisting of anosmic hypogonadotropic hypogonadism (Kallmann syndrome, KS) and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). KS is genetically heterogeneous. We hereby present 5 young male patients with GnRH deficiency caused by mutations in the KAL1 gene. Read More

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February 2016

Snapin interacts with G-protein coupled receptor PKR2.

Biochem Biophys Res Commun 2016 Jan 11;469(3):501-6. Epub 2015 Dec 11.

The State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, Hunan, China. Electronic address:

Mutations in Prokineticin receptor 2 (PKR2), a G-protein-coupled receptor, have been identified in patients with Kallmann syndrome and/or idiopathic hypogonadotropic hypogonadism, characterized by delayed puberty and infertility. In this study, we performed yeast two-hybrid screening by using PKR2 C-terminus (amino acids 333-384) as a bait, and identified Snapin as a novel interaction partner for PKR2. The interaction of Snapin and PKR2 was confirmed in GST pull-down and co-immunoprecipitation studies. Read More

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January 2016