The extracellular thyrotropin receptor domain is not a major candidate for mutations in toxic thyroid nodules

被引:17
作者
Fuhrer, D
Kubisch, C
Scheibler, U
Lamesch, P
Krohn, K
Paschke, R
机构
[1] Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany
[2] Parkkrankenhaus Dosen, Dept Surg, Leipzig, Germany
[3] Univ Leipzig, Dept Surg 2, Leipzig, Germany
关键词
D O I
10.1089/thy.1998.8.997
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Constitutive activation of the cyclic adenosine monophosphate (cAMP) cascade by either thyrotropin receptor (TSHR) or gsp mutations is considered to be the major molecular cause of toxic thyroid nodules (TTNs). In a recent study we investigated a consecutive series of 31 TTNs and identified 15 somatic TSHR mutations (n = 14 in exon 10; n 1 in exon 9) but no mutations in gsp exons 7-10 (3). The purpose of the present study was to determine whether the extracellular TSHR domain would be a candidate for mutations causing TTNs. Therefore, we screened TSHR exons 1-8 in the remaining 16 TTNs without mutations in TSHR exons 9 and 10 and gsp exons 7-10 of our previous study. Except for a known functional polymorphism in exon 1 (Pro 52 Thr) in 2 TTNs and a silent base exchange in exon 7 (187 Asn) in 7 other TTNs no TSHR mutations were identified. To clarify the molecular etiology of TTNs without TSHR or gsp mutations, candidate genes. in other steps of the cAMP cascade have to be considered.
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收藏
页码:997 / 1001
页数:5
相关论文
共 33 条
  • [1] A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism
    DeRoux, N
    Polak, M
    Couet, J
    Leger, J
    Czernichow, P
    Milgrom, E
    Misrahi, M
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (06) : 2023 - 2026
  • [2] Microsatellites and PCR primers for genetic studies and genomic sequencing of the human TSH receptor gene
    deRoux, N
    Misrahi, M
    Chatelain, N
    Gross, B
    Milgrom, E
    [J]. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1996, 117 (02) : 253 - 256
  • [3] Two autonomous nodules of a patient with multinodular goiter harbor different activating mutations of the thyrotropin receptor gene
    Duprez, L
    Hermans, J
    VanSande, J
    Dumont, JE
    Vassart, G
    Parma, J
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (01) : 306 - 308
  • [4] GERMLINE MUTATIONS IN THE THYROTROPIN RECEPTOR GENE CAUSE NON-AUTOIMMUNE AUTOSOMAL-DOMINANT HYPERTHYROIDISM
    DUPREZ, L
    PARMA, J
    VANSANDE, J
    ALLGEIER, A
    LECLERE, J
    SCHVARTZ, C
    DELISLE, MJ
    DECOULX, M
    ORGIAZZI, J
    DUMONT, J
    VASSART, G
    [J]. NATURE GENETICS, 1994, 7 (03) : 396 - 401
  • [5] ESAPA CT, 1996, J ENDOCRINOL INVEST, V19, P71
  • [6] Somatic mutations in the thyrotropin receptor gene and not in the G(s)alpha protein gene in 31 toxic thyroid nodules
    Fuhrer, D
    Holzapfel, HP
    Wonerow, P
    Scherbaum, WA
    Paschke, R
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (11) : 3885 - 3891
  • [7] Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism
    Führer, D
    Wonerow, P
    Willgerodt, H
    Paschke, R
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (12) : 4234 - 4238
  • [8] Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene
    Holzapfel, HP
    Wonerow, P
    vonPetrykowski, W
    Henschen, M
    Scherbaum, WA
    Paschke, R
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (11) : 3879 - 3884
  • [9] Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (Serine281->Isoleucine) in the extracellular domain of the thyrotropin receptor
    Kopp, P
    Muirhead, S
    Jourdain, N
    Gu, WX
    Jameson, JL
    Rodd, C
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (06) : 1634 - 1639
  • [10] BRIEF REPORT - CONGENITAL HYPERTHYROIDISM CAUSED BY A MUTATION IN THE THYROTROPIN-RECEPTOR GENE
    KOPP, P
    VANSANDE, J
    PARMA, J
    DUPREZ, L
    GERBER, H
    JOSS, E
    JAMESON, JL
    DUMONT, JE
    VASSART, G
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (03) : 150 - 154