A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and choreoathetosis

part of the spectrum of brain-thyroid-lung syndrome

Scott Williamson (Lead / Corresponding author), Martin Kirkpatrick, Stephen Greene, David Goudie

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    The NKX2-1 (TTF-1 or TITF-1) gene on chromosome 14q13 codes for the thyroid transcription factor 1 (TTF-1). It is expressed in the developing brain, lung, and thyroid. Defects have been associated with chorea, hypothyroidism, and lung disease, comprising the "brain-thyroid-lung syndrome." We describe here 3 cases of novel missense mutation (c.626G>C; p.Arg209Pro) in NKX2-1 in 2 generations of a nonconsanguinous family. Firstly 2 sons were affected by childhood-onset hypothyroidism and a movement disorder characterized by ataxia in the early years followed by the emergence of a superimposed chorea. The mutation was also found in the granddaughter, when she presented with the same clinical features. We hypothesize that the mutation arose as a result of gonadal mosaicism, as the mutation was not detected in leucocyte DNA from either grandparent. The features are consistent with a diagnosis of Brain-thyroid-lung syndrome, which previously could have been classified as benign hereditary chorea with hypothyroidism.
    Original languageEnglish
    Pages (from-to)666-669
    Number of pages4
    JournalJournal of Child Neurology
    Volume29
    Issue number5
    DOIs
    Publication statusPublished - May 2014

    Fingerprint

    Chorea
    Hypothyroidism
    Mutation
    Mosaicism
    Movement Disorders
    Missense Mutation
    Ataxia
    Nuclear Family
    Lung Diseases
    Thyroid Gland
    Leukocytes
    Chromosomes
    Lung
    DNA
    Brain
    Genes
    Choreoathetosis, Hypothyroidism, And Neonatal Respiratory Distress
    thyroid nuclear factor 1

    Cite this

    Williamson, Scott ; Kirkpatrick, Martin ; Greene, Stephen ; Goudie, David. / A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and choreoathetosis : part of the spectrum of brain-thyroid-lung syndrome. In: Journal of Child Neurology. 2014 ; Vol. 29, No. 5. pp. 666-669.
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    abstract = "The NKX2-1 (TTF-1 or TITF-1) gene on chromosome 14q13 codes for the thyroid transcription factor 1 (TTF-1). It is expressed in the developing brain, lung, and thyroid. Defects have been associated with chorea, hypothyroidism, and lung disease, comprising the {"}brain-thyroid-lung syndrome.{"} We describe here 3 cases of novel missense mutation (c.626G>C; p.Arg209Pro) in NKX2-1 in 2 generations of a nonconsanguinous family. Firstly 2 sons were affected by childhood-onset hypothyroidism and a movement disorder characterized by ataxia in the early years followed by the emergence of a superimposed chorea. The mutation was also found in the granddaughter, when she presented with the same clinical features. We hypothesize that the mutation arose as a result of gonadal mosaicism, as the mutation was not detected in leucocyte DNA from either grandparent. The features are consistent with a diagnosis of Brain-thyroid-lung syndrome, which previously could have been classified as benign hereditary chorea with hypothyroidism.",
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    A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and choreoathetosis : part of the spectrum of brain-thyroid-lung syndrome. / Williamson, Scott (Lead / Corresponding author); Kirkpatrick, Martin; Greene, Stephen; Goudie, David.

    In: Journal of Child Neurology, Vol. 29, No. 5, 05.2014, p. 666-669.

    Research output: Contribution to journalArticle

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