Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH

Jun Xie, Silvana Pannain, Joachim Pohlenz, Roy E Weiss, Kathleen Moltz, Michel Morlot, Carmela Asteria, Luca Persani, Paolo Beck-Peccoz, Jasmine Parma, Gilbert Vassart, Samuel Refetoff

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Resistance to TSH (RTSH) is a recently described syndrome of reduced sensitivity to TSH that manifests as euthyroid hyperthyrotropinemia. It is usually identified at birth during routine neonatal screening for congenital hypothyroidism. In less than 2 yr, 13 subjects with RTSH belonging to 8 families have been reported, and all were shown to harbor mutations in the TSH receptor (TSHR) gene. We now report the occurrence of RTSH in 3 unrelated families. Contrary to previous reports, the inheritance of RTSH in 2 of the families was dominant rather than recessive and was not associated with abnormalities in the TSHR gene. Abnormalities in the TSHR gene were excluded by sequencing all coding sequences, exon/intron junctions, and the promoter region of the gene. Furthermore, the involvement of the TSHR in the manifestation of the RTSH phenotype was excluded in 2 families by linkage analysis using intragenic polymorphic markers. We excluded defects in the TSH β-subunit by sequencing its gene and by showing that the circulating TSH in affected subjects from all families had normal bioactivity. Also, no abnormalities were found in the G(s)α gene of one family analyzed by GC- clamped denaturing gradient gel electrophoresis. This study shows that RTSH may be a manifestation of several different genetic defects that requires the exploration of other candidate genes involved in the TSH-TSHR-G(s)α cascade and genes participating in its regulation.

Original languageEnglish (US)
Pages (from-to)3933-3940
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume82
Issue number12
StatePublished - 1997
Externally publishedYes

Fingerprint

Thyrotropin Receptors
Thyrotropin
Genes
Mutation
Neonatal Screening
Congenital Hypothyroidism
Denaturing Gradient Gel Electrophoresis
Defects
Ports and harbors
Bioactivity
Electrophoresis
Genetic Promoter Regions
Introns
Exons
Screening
Gels
Parturition
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH. / Xie, Jun; Pannain, Silvana; Pohlenz, Joachim; Weiss, Roy E; Moltz, Kathleen; Morlot, Michel; Asteria, Carmela; Persani, Luca; Beck-Peccoz, Paolo; Parma, Jasmine; Vassart, Gilbert; Refetoff, Samuel.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 82, No. 12, 1997, p. 3933-3940.

Research output: Contribution to journalArticle

Xie, J, Pannain, S, Pohlenz, J, Weiss, RE, Moltz, K, Morlot, M, Asteria, C, Persani, L, Beck-Peccoz, P, Parma, J, Vassart, G & Refetoff, S 1997, 'Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH', Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 12, pp. 3933-3940.
Xie, Jun ; Pannain, Silvana ; Pohlenz, Joachim ; Weiss, Roy E ; Moltz, Kathleen ; Morlot, Michel ; Asteria, Carmela ; Persani, Luca ; Beck-Peccoz, Paolo ; Parma, Jasmine ; Vassart, Gilbert ; Refetoff, Samuel. / Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH. In: Journal of Clinical Endocrinology and Metabolism. 1997 ; Vol. 82, No. 12. pp. 3933-3940.
@article{2e6045463a4b4818970a7ebb70045b72,
title = "Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH",
abstract = "Resistance to TSH (RTSH) is a recently described syndrome of reduced sensitivity to TSH that manifests as euthyroid hyperthyrotropinemia. It is usually identified at birth during routine neonatal screening for congenital hypothyroidism. In less than 2 yr, 13 subjects with RTSH belonging to 8 families have been reported, and all were shown to harbor mutations in the TSH receptor (TSHR) gene. We now report the occurrence of RTSH in 3 unrelated families. Contrary to previous reports, the inheritance of RTSH in 2 of the families was dominant rather than recessive and was not associated with abnormalities in the TSHR gene. Abnormalities in the TSHR gene were excluded by sequencing all coding sequences, exon/intron junctions, and the promoter region of the gene. Furthermore, the involvement of the TSHR in the manifestation of the RTSH phenotype was excluded in 2 families by linkage analysis using intragenic polymorphic markers. We excluded defects in the TSH β-subunit by sequencing its gene and by showing that the circulating TSH in affected subjects from all families had normal bioactivity. Also, no abnormalities were found in the G(s)α gene of one family analyzed by GC- clamped denaturing gradient gel electrophoresis. This study shows that RTSH may be a manifestation of several different genetic defects that requires the exploration of other candidate genes involved in the TSH-TSHR-G(s)α cascade and genes participating in its regulation.",
author = "Jun Xie and Silvana Pannain and Joachim Pohlenz and Weiss, {Roy E} and Kathleen Moltz and Michel Morlot and Carmela Asteria and Luca Persani and Paolo Beck-Peccoz and Jasmine Parma and Gilbert Vassart and Samuel Refetoff",
year = "1997",
language = "English (US)",
volume = "82",
pages = "3933--3940",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "12",

}

TY - JOUR

T1 - Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH

AU - Xie, Jun

AU - Pannain, Silvana

AU - Pohlenz, Joachim

AU - Weiss, Roy E

AU - Moltz, Kathleen

AU - Morlot, Michel

AU - Asteria, Carmela

AU - Persani, Luca

AU - Beck-Peccoz, Paolo

AU - Parma, Jasmine

AU - Vassart, Gilbert

AU - Refetoff, Samuel

PY - 1997

Y1 - 1997

N2 - Resistance to TSH (RTSH) is a recently described syndrome of reduced sensitivity to TSH that manifests as euthyroid hyperthyrotropinemia. It is usually identified at birth during routine neonatal screening for congenital hypothyroidism. In less than 2 yr, 13 subjects with RTSH belonging to 8 families have been reported, and all were shown to harbor mutations in the TSH receptor (TSHR) gene. We now report the occurrence of RTSH in 3 unrelated families. Contrary to previous reports, the inheritance of RTSH in 2 of the families was dominant rather than recessive and was not associated with abnormalities in the TSHR gene. Abnormalities in the TSHR gene were excluded by sequencing all coding sequences, exon/intron junctions, and the promoter region of the gene. Furthermore, the involvement of the TSHR in the manifestation of the RTSH phenotype was excluded in 2 families by linkage analysis using intragenic polymorphic markers. We excluded defects in the TSH β-subunit by sequencing its gene and by showing that the circulating TSH in affected subjects from all families had normal bioactivity. Also, no abnormalities were found in the G(s)α gene of one family analyzed by GC- clamped denaturing gradient gel electrophoresis. This study shows that RTSH may be a manifestation of several different genetic defects that requires the exploration of other candidate genes involved in the TSH-TSHR-G(s)α cascade and genes participating in its regulation.

AB - Resistance to TSH (RTSH) is a recently described syndrome of reduced sensitivity to TSH that manifests as euthyroid hyperthyrotropinemia. It is usually identified at birth during routine neonatal screening for congenital hypothyroidism. In less than 2 yr, 13 subjects with RTSH belonging to 8 families have been reported, and all were shown to harbor mutations in the TSH receptor (TSHR) gene. We now report the occurrence of RTSH in 3 unrelated families. Contrary to previous reports, the inheritance of RTSH in 2 of the families was dominant rather than recessive and was not associated with abnormalities in the TSHR gene. Abnormalities in the TSHR gene were excluded by sequencing all coding sequences, exon/intron junctions, and the promoter region of the gene. Furthermore, the involvement of the TSHR in the manifestation of the RTSH phenotype was excluded in 2 families by linkage analysis using intragenic polymorphic markers. We excluded defects in the TSH β-subunit by sequencing its gene and by showing that the circulating TSH in affected subjects from all families had normal bioactivity. Also, no abnormalities were found in the G(s)α gene of one family analyzed by GC- clamped denaturing gradient gel electrophoresis. This study shows that RTSH may be a manifestation of several different genetic defects that requires the exploration of other candidate genes involved in the TSH-TSHR-G(s)α cascade and genes participating in its regulation.

UR - http://www.scopus.com/inward/record.url?scp=9844223914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9844223914&partnerID=8YFLogxK

M3 - Article

VL - 82

SP - 3933

EP - 3940

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -