Clinical and molecular characterization of a large sample of patients with hypogonadotropic hypogonadism

Bhagavath, Bala; Podolsky, Robert H.; Özata, Metịn; Bolu, Erol; Bick, David; Kulharya, Anita S.; Sherins, Richard J.; Layman, Lawrence C.

doi:10.1016/j.fertnstert.2005.08.044

Cited by 104 publications

(101 citation statements)

References 32 publications

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“…Affected males had serum testosterone levels less than 100ng/dL (normal: 300-1100ng/dL), whereas females had absent breast development and M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Quaynor et al 7 hypoestrogenic amenorrhea (Bhagavath et al, 2006). MRI of the brain and pituitary was normal.…”

Section: Patientsmentioning

confidence: 99%

“…Hypogonadotropic hypogonadism was defined as the absence of puberty (age 17 in females; 18 in males) with low/normal FSH and LH levels (Bhagavath et al, 2006). Affected males had serum testosterone levels less than 100ng/dL (normal: 300-1100ng/dL), whereas females had absent breast development and M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Quaynor et al 7 hypoestrogenic amenorrhea (Bhagavath et al, 2006).…”

Section: Patientsmentioning

confidence: 99%

“…MRI of the brain and pituitary was normal. Serum prolactin, thyroid stimulating hormone (TSH), thyroxine (T4), and cortisol were normal (Bhagavath et al, 2006). Patients characterized as nHH exhibited a normal sense of smell by the Smell Identification Test or by history, while those with KS had absent or decreased sense of smell (Quaynor et al, 2011).…”

Section: Patientsmentioning

confidence: 99%

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Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome

Quaynor

Bosley

Duckworth

et al. 2016

Molecular and Cellular Endocrinology

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Targeted next generation sequencing approach identifies nineteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann Syndrome, Molecular and Cellular Endocrinology (2016), doi: 10.1016/ j.mce.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe genetic basis is unknown for ~60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 19 new candidate genes including:

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Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

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Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome

Quaynor

Bosley

Duckworth

et al. 2016

Molecular and Cellular Endocrinology

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“…In two large screening studies, mutations in the coding sequence of the GnRH receptor were identified in 10.4 and 3.5% of cases with nIHH [5, 6]. Additionally, it has recently been shown that loss-of-function mutations of the G protein-coupled receptor, GPR54 , lead to nIHH in a few cases [7].…”

Section: Introductionmentioning

confidence: 99%

Molecular Genetic Analysis of Normosmic Hypogonadotropic Hypogonadism in a Turkish Population: Identification and Detailed Functional Characterization of a Novel Mutation in the Gonadotropin-Releasing Hormone Receptor Gene

Topaloğlu

Lu²,

Farooqi³

et al. 2006

Neuroendocrinology

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Background/Aims: Currently known mutations account for less than 15% of cases with normosmic hypogonadotropic hypogonadism (nIHH). The objective of the study was to identify novel hereditary associations in the pathogenesis of nIHH. Methods: We investigated 26 Turkish patients with nIHH (21 males and 5 females) from 22 families. The coding regions of the GnRH receptor, GnRH1, GPR54, and KISS1 genes were directly sequenced. Results: In two sisters, a novel homozygous missense mutation, R139C, located in the conserved DRS motif at the junction of the third transmembrane and the second intracellular loop of the GnRH receptor was identified. The R139C mutation almost completely abolished plasma membrane expression while having little effect on GnRH-binding affinity. The mutant receptor expression was rescued by a membrane-permeant, non-peptide GnRH receptor antagonist IN3. Conclusions: Consistent with the previous studies we were able to find mutations in only 7.6% of a well-defined group of patients with nIHH, which further suggests that yet unidentified genetic associations to explain nIHH exist.

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“…Chromosome study in the cases with hypogonadism becomes essential from the clinical point of view. Bhagavath et al [3] karyotyped 76 HH patients and identified a sporadic male patient with complete HH and hyposmia who had a balanced chromosome translocation, reported as 46,XY,t(10;12) (q26.3;q13.1). Four cases reported of (X;Y) translocations with a derivative Y.…”

Section: Discussionmentioning

confidence: 99%

The Frequency and Types of Chromosomal Aberrations in the Patients with Hypogonadism

2015

Human Genet Embryol

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Objectives: Hypogonadism is the clinical manifestation of the impaired function of the testes and the ovaries, and is either due to endocrinological problems or chromosomal abnornlalities (CA). Chromosomal analysis is one important piece in the hypogonadism individuals, and becomes essential from the clinical point of view. Design:To determine the frequency, types of CAs in a hypogonadism population. Materials and method:The current study was a retrospective analysis to examine the CAs and prevalence in 64 cases with unexplained hypogonadism problem. The samples were cultured routinely for the karyotype analysis using G banding. Results:A total of 64 individuals with infertility was analysed. The karyotype results were normal in 52 (81.2%) of 64 individuals. However, CAs were detected in 12 (18.8%) of all individuals. The 15.6% of these CAs was numerical aberrations, and also structural CA was 3.1%. Specifically, Klinefelter syndrome (KS) was the most common karyotype (14.1%,9 cases) among the all cases, followed by 46,XX,anoploidy; 46,Xi(Xq) and 46,XY,robt(14;15). Conclusion:We found a high rate CAs (18.8%) in patients with hypogonadism. Therefore, cytogenetic analysis can be strongly recommended in hypogonadism individuals, and should be performed routinely in both the male and female with hypogonadism.

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Clinical and molecular characterization of a large sample of patients with hypogonadotropic hypogonadism

Cited by 104 publications

References 32 publications

Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome

Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome

Molecular Genetic Analysis of Normosmic Hypogonadotropic Hypogonadism in a Turkish Population: Identification and Detailed Functional Characterization of a Novel Mutation in the Gonadotropin-Releasing Hormone Receptor Gene

The Frequency and Types of Chromosomal Aberrations in the Patients with Hypogonadism

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