Molecular and gene network analysis of thyroid transcription factor 1 (TTF1) and enhanced at puberty (EAP1) genes in patients with GnRH-dependent pubertal disorders

Priscilla Cukier, Hollis Wright, Tomke Rulfs, Leticia Ferreira Gontijo Silveira, Milena Gurgel Teles, Berenice Bilharinho Mendonca, Ivo J P Arnhold, Sabine Heger, Ana Claudia Latronico, Sergio Ojeda, Vinicius Nahime Brito

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    Background/Aim: TTF1 and EAP1 are transcription factors that modulate gonadotropin-releasing hormone expression. We investigated the contribution of TTF1 and EAP1 genes to central pubertal disorders. Patients and Methods: 133 patients with central pubertal disorders were studied: 86 with central precocious puberty and 47 with normosmic isolated hypogonadotropic hypogonadism. The coding region of TTF1 and EAP1 were sequenced. Variations of polyglutamine and polyalanine repeats in EAP1 were analyzed by GeneScan software. Association of TTF1 and EAP1 to genes implicated in timing of puberty was investigated by meta-network framework GeneMANIA and Cytoscape software. Results: Direct sequencing of the TTF1 did not reveal any mutation or polymorphisms. Four EAP1 synonymous variants were identified with similar frequencies among groups. The most common EAP1 5′-distal polyalanine genotype was the homozygous 12/12, but the genotype 12/9 was identified in 2 central precocious puberty sisters without functional alteration in EAP1 transcriptional activity. TTF1 and EAP1 were connected, via genetic networks, to genes implicated in the control of menarche. Conclusion: No TTF1 or EAP1 germline mutations were associated with central pubertal disorders. TTF1 and EAP1 may affect puberty by changing expression in response to other members of puberty-associated gene networks, or by differentially affecting the expression of gene components of these networks.

    Original languageEnglish (US)
    Pages (from-to)257-266
    Number of pages10
    JournalHormone Research in Paediatrics
    Volume80
    Issue number4
    DOIs
    StatePublished - Oct 2013

    Fingerprint

    Gene Regulatory Networks
    Puberty
    Gonadotropin-Releasing Hormone
    Genes
    Software
    Genotype
    Gene Components
    Menarche
    Hypogonadism
    thyroid nuclear factor 1
    Germ-Line Mutation
    Siblings
    Transcription Factors
    Mutation

    Keywords

    • Central precocious puberty
    • EAP1
    • Hypogonadotropic hypogonadism
    • Hypothalamic hamartoma
    • TTF1

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism
    • Pediatrics, Perinatology, and Child Health

    Cite this

    Molecular and gene network analysis of thyroid transcription factor 1 (TTF1) and enhanced at puberty (EAP1) genes in patients with GnRH-dependent pubertal disorders. / Cukier, Priscilla; Wright, Hollis; Rulfs, Tomke; Silveira, Leticia Ferreira Gontijo; Teles, Milena Gurgel; Mendonca, Berenice Bilharinho; Arnhold, Ivo J P; Heger, Sabine; Latronico, Ana Claudia; Ojeda, Sergio; Brito, Vinicius Nahime.

    In: Hormone Research in Paediatrics, Vol. 80, No. 4, 10.2013, p. 257-266.

    Research output: Contribution to journalArticle

    Cukier, P, Wright, H, Rulfs, T, Silveira, LFG, Teles, MG, Mendonca, BB, Arnhold, IJP, Heger, S, Latronico, AC, Ojeda, S & Brito, VN 2013, 'Molecular and gene network analysis of thyroid transcription factor 1 (TTF1) and enhanced at puberty (EAP1) genes in patients with GnRH-dependent pubertal disorders', Hormone Research in Paediatrics, vol. 80, no. 4, pp. 257-266. https://doi.org/10.1159/000354643
    Cukier, Priscilla ; Wright, Hollis ; Rulfs, Tomke ; Silveira, Leticia Ferreira Gontijo ; Teles, Milena Gurgel ; Mendonca, Berenice Bilharinho ; Arnhold, Ivo J P ; Heger, Sabine ; Latronico, Ana Claudia ; Ojeda, Sergio ; Brito, Vinicius Nahime. / Molecular and gene network analysis of thyroid transcription factor 1 (TTF1) and enhanced at puberty (EAP1) genes in patients with GnRH-dependent pubertal disorders. In: Hormone Research in Paediatrics. 2013 ; Vol. 80, No. 4. pp. 257-266.
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    title = "Molecular and gene network analysis of thyroid transcription factor 1 (TTF1) and enhanced at puberty (EAP1) genes in patients with GnRH-dependent pubertal disorders",
    abstract = "Background/Aim: TTF1 and EAP1 are transcription factors that modulate gonadotropin-releasing hormone expression. We investigated the contribution of TTF1 and EAP1 genes to central pubertal disorders. Patients and Methods: 133 patients with central pubertal disorders were studied: 86 with central precocious puberty and 47 with normosmic isolated hypogonadotropic hypogonadism. The coding region of TTF1 and EAP1 were sequenced. Variations of polyglutamine and polyalanine repeats in EAP1 were analyzed by GeneScan software. Association of TTF1 and EAP1 to genes implicated in timing of puberty was investigated by meta-network framework GeneMANIA and Cytoscape software. Results: Direct sequencing of the TTF1 did not reveal any mutation or polymorphisms. Four EAP1 synonymous variants were identified with similar frequencies among groups. The most common EAP1 5′-distal polyalanine genotype was the homozygous 12/12, but the genotype 12/9 was identified in 2 central precocious puberty sisters without functional alteration in EAP1 transcriptional activity. TTF1 and EAP1 were connected, via genetic networks, to genes implicated in the control of menarche. Conclusion: No TTF1 or EAP1 germline mutations were associated with central pubertal disorders. TTF1 and EAP1 may affect puberty by changing expression in response to other members of puberty-associated gene networks, or by differentially affecting the expression of gene components of these networks.",
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    author = "Priscilla Cukier and Hollis Wright and Tomke Rulfs and Silveira, {Leticia Ferreira Gontijo} and Teles, {Milena Gurgel} and Mendonca, {Berenice Bilharinho} and Arnhold, {Ivo J P} and Sabine Heger and Latronico, {Ana Claudia} and Sergio Ojeda and Brito, {Vinicius Nahime}",
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    AU - Wright, Hollis

    AU - Rulfs, Tomke

    AU - Silveira, Leticia Ferreira Gontijo

    AU - Teles, Milena Gurgel

    AU - Mendonca, Berenice Bilharinho

    AU - Arnhold, Ivo J P

    AU - Heger, Sabine

    AU - Latronico, Ana Claudia

    AU - Ojeda, Sergio

    AU - Brito, Vinicius Nahime

    PY - 2013/10

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    N2 - Background/Aim: TTF1 and EAP1 are transcription factors that modulate gonadotropin-releasing hormone expression. We investigated the contribution of TTF1 and EAP1 genes to central pubertal disorders. Patients and Methods: 133 patients with central pubertal disorders were studied: 86 with central precocious puberty and 47 with normosmic isolated hypogonadotropic hypogonadism. The coding region of TTF1 and EAP1 were sequenced. Variations of polyglutamine and polyalanine repeats in EAP1 were analyzed by GeneScan software. Association of TTF1 and EAP1 to genes implicated in timing of puberty was investigated by meta-network framework GeneMANIA and Cytoscape software. Results: Direct sequencing of the TTF1 did not reveal any mutation or polymorphisms. Four EAP1 synonymous variants were identified with similar frequencies among groups. The most common EAP1 5′-distal polyalanine genotype was the homozygous 12/12, but the genotype 12/9 was identified in 2 central precocious puberty sisters without functional alteration in EAP1 transcriptional activity. TTF1 and EAP1 were connected, via genetic networks, to genes implicated in the control of menarche. Conclusion: No TTF1 or EAP1 germline mutations were associated with central pubertal disorders. TTF1 and EAP1 may affect puberty by changing expression in response to other members of puberty-associated gene networks, or by differentially affecting the expression of gene components of these networks.

    AB - Background/Aim: TTF1 and EAP1 are transcription factors that modulate gonadotropin-releasing hormone expression. We investigated the contribution of TTF1 and EAP1 genes to central pubertal disorders. Patients and Methods: 133 patients with central pubertal disorders were studied: 86 with central precocious puberty and 47 with normosmic isolated hypogonadotropic hypogonadism. The coding region of TTF1 and EAP1 were sequenced. Variations of polyglutamine and polyalanine repeats in EAP1 were analyzed by GeneScan software. Association of TTF1 and EAP1 to genes implicated in timing of puberty was investigated by meta-network framework GeneMANIA and Cytoscape software. Results: Direct sequencing of the TTF1 did not reveal any mutation or polymorphisms. Four EAP1 synonymous variants were identified with similar frequencies among groups. The most common EAP1 5′-distal polyalanine genotype was the homozygous 12/12, but the genotype 12/9 was identified in 2 central precocious puberty sisters without functional alteration in EAP1 transcriptional activity. TTF1 and EAP1 were connected, via genetic networks, to genes implicated in the control of menarche. Conclusion: No TTF1 or EAP1 germline mutations were associated with central pubertal disorders. TTF1 and EAP1 may affect puberty by changing expression in response to other members of puberty-associated gene networks, or by differentially affecting the expression of gene components of these networks.

    KW - Central precocious puberty

    KW - EAP1

    KW - Hypogonadotropic hypogonadism

    KW - Hypothalamic hamartoma

    KW - TTF1

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