Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations
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{"title"=>"Reversible congenital hypogonadotropic hypogonadism in patients with CHD7, FGFR1 or GNRHR mutations", "type"=>"journal", "authors"=>[{"first_name"=>"Eeva Maria", "last_name"=>"Laitinen", "scopus_author_id"=>"35976131200"}, {"first_name"=>"Johanna", "last_name"=>"Tommiska", "scopus_author_id"=>"8638857600"}, {"first_name"=>"Timo", "last_name"=>"Sane", "scopus_author_id"=>"7003899208"}, {"first_name"=>"Kirsi", "last_name"=>"Vaaralahti", "scopus_author_id"=>"35293868200"}, {"first_name"=>"Jorma", "last_name"=>"Toppari", "scopus_author_id"=>"35479112600"}, {"first_name"=>"Taneli", "last_name"=>"Raivio", "scopus_author_id"=>"7004326920"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84862549630", "pui"=>"365049399", "doi"=>"10.1371/journal.pone.0039450", "sgr"=>"84862549630", "pmid"=>"22724017", "issn"=>"19326203"}, "id"=>"ce687f1b-beb6-3b44-b95b-dc0dfe9a3c87", "abstract"=>"BACKGROUND: Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features.\\n\\nMETHODS AND FINDINGS: Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18-61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHβ were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21-39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q), which was accompanied by another GNRHR mutation (R139H or del309F). In addition, both of the KS patients had a mutation in CHD7 (p.Q51X) or FGFR1 (c.91+2T>A).\\n\\nCONCLUSIONS: Considerable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal.", "link"=>"http://www.mendeley.com/research/reversible-congenital-hypogonadotropic-hypogonadism-patients-chd7-fgfr1-gnrhr-mutations", "reader_count"=>21, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Master"=>2, "Other"=>4, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Master"=>2, "Other"=>4, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>10, "Veterinary Science and Veterinary Medicine"=>1, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Italy"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/621897"], "description"=>"<p>Schematic depicting time of diagnosis, treatment history, and reversal in 6 men with congenital hypogonadotropic hypogonadism.</p>", "links"=>[], "tags"=>["depicting", "reversal", "men", "congenital", "hypogonadotropic"], "article_id"=>292385, "categories"=>["Chemistry", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eeva-Maria Laitinen", "Johanna Tommiska", "Timo Sane", "Kirsi Vaaralahti", "Jorma Toppari", "Taneli Raivio"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039450.g002", "stats"=>{"downloads"=>4, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_depicting_time_of_diagnosis_treatment_history_and_reversal_in_6_men_with_congenital_hypogonadotropic_hypogonadism_/292385", "title"=>"Schematic depicting time of diagnosis, treatment history, and reversal in 6 men with congenital hypogonadotropic hypogonadism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-19 00:39:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/323589"], "description"=>"<div><h3>Background</h3><p>Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features.</p> <h3>Methods and Findings</h3><p>Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18–61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. <em>KAL1</em>, <em>FGFR1</em>, <em>FGF8</em>, <em>PROK2</em>, <em>PROKR2</em>, <em>CHD7</em>, <em>WDR11</em>, <em>GNRHR</em>, <em>GNRH1</em>, <em>KISS1R</em>, <em>KISS1</em>, <em>TAC3</em>, <em>TACR3</em>, and <em>LHβ</em> were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21–39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same <em>GNRHR</em> mutation (R262Q), which was accompanied by another <em>GNRHR</em> mutation (R139H or del309F). In addition, both of the KS patients had a mutation in <em>CHD7</em> (p.Q51X) or <em>FGFR1</em> (c.91+2T>A).</p> <h3>Conclusions</h3><p>Considerable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the <em>GNRHR</em> mutation R262Q accompanied by another <em>GNRHR</em> mutation may be prone to reversal, although even patients with a truncating mutation in <em>CHD7</em> or a splice-site mutation in <em>FGFR1</em> can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal.</p> </div>", "links"=>[], "tags"=>["reversible", "congenital", "hypogonadotropic", "hypogonadism", "patients", "mutations"], "article_id"=>123861, "categories"=>["Chemistry", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eeva-Maria Laitinen", "Johanna Tommiska", "Timo Sane", "Kirsi Vaaralahti", "Jorma Toppari", "Taneli Raivio"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039450", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Reversible_Congenital_Hypogonadotropic_Hypogonadism_in_Patients_with_CHD7_FGFR1_or_GNRHR_Mutations/123861", "title"=>"Reversible Congenital Hypogonadotropic Hypogonadism in Patients with <em>CHD7</em>, <em>FGFR1</em> or <em>GNRHR</em> Mutations", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-19 01:04:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/621958"], "description"=>"<p>Tvol, testicular volume; KS, Kallmann Syndrome; nHH, normosmic HH. Normal adult men reference range for testosterone (T) 10–38 nmol/L, for luteinizing hormone (LH) 1.7-8.6 IU/L, and for follicle-stimulating hormone (FSH) 1.5-12.4 IU/L.</p>", "links"=>[], "tags"=>["biochemical", "patients", "congenital", "hypogonadotropic", "hypogonadism", "reversal"], "article_id"=>292446, "categories"=>["Chemistry", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eeva-Maria Laitinen", "Johanna Tommiska", "Timo Sane", "Kirsi Vaaralahti", "Jorma Toppari", "Taneli Raivio"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039450.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_and_biochemical_features_of_patients_with_congenital_hypogonadotropic_hypogonadism_HH_before_and_after_reversal_of_HH_/292446", "title"=>"Clinical and biochemical features of patients with congenital hypogonadotropic hypogonadism (HH) before and after reversal of HH.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-19 00:40:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/621791"], "description"=>"<p>Mean testicular volumes of HH patients were measured at the time of the diagnosis (solid circles) and at participation in the current study (small line). We used the value 2 mL for testicular volumes for cases #2, #6, #7, and #19 at diagnosis, because volumes were estimated to be “small\" or “prepubertal\" in medical records. Cases #21–25 were previously treated with recombinant-FSH and hCG to induce spermatogenesis. Seven patients (cases #1, 4, 6–9, and 26) discontinued hormone therapy, and 6 (cases #1–6) showed reversal of HH (4 during the treatment pause and 2 without TRT). In addition, #11, 13, 18, and 21 had spontaneous testis growth but they refused to discontinue TRT.</p>", "links"=>[], "tags"=>["reversal", "congenital", "hypogonadotropic", "hypogonadism"], "article_id"=>292278, "categories"=>["Chemistry", "Biological Sciences", "Genetics", "Medicine"], "users"=>["Eeva-Maria Laitinen", "Johanna Tommiska", "Timo Sane", "Kirsi Vaaralahti", "Jorma Toppari", "Taneli Raivio"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039450.g001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Assessment_of_the_reversal_of_congenital_hypogonadotropic_hypogonadism_HH_/292278", "title"=>"Assessment of the reversal of congenital hypogonadotropic hypogonadism (HH).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-19 00:37:58"}

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Relative Metric

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