Congenital Central Isolated Hypothyroidism Caused by a Homozygous Mutation in the TSH-β Subunit Gene
| Autor: | Samuel Refetoff, G. Van Vliet, Claudine Heinrichs, Pierre Bergmann, Laurence Duprez, Neal H. Scherberg, Pierre Bourdoux, François Delange, Jasmine Parma, Gilbert Vassart |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
endocrine system
medicine.medical_specialty Adolescent endocrine system diseases Endocrinology Diabetes and Metabolism Molecular Sequence Data Population Levothyroxine Thyrotropin Frameshift mutation Endocrinology Hypothyroidism Internal medicine Congenital Hypothyroidism medicine Humans Amino Acid Sequence education education.field_of_study Base Sequence biology Homozygote DNA medicine.disease Prolactin Congenital hypothyroidism Polyclonal antibodies Mutation biology.protein Female Antibody hormones hormone substitutes and hormone antagonists ATP synthase alpha/beta subunits medicine.drug |
| Zdroj: | Thyroid. 10:387-391 |
| ISSN: | 1557-9077 1050-7256 |
| DOI: | 10.1089/thy.2000.10.387 |
| Popis: | We report a Belgian girl born in 1983 with isolated thyrotropin (TSH) deficiency. Hypothyroidism without goiter was diagnosed at the age of 2 months, with extremely low total thyroxine (T4) at 0.3 microg/dL (4 nmol/L; N[normal]: 5.6-11.4 microg/dL). Basal TSH, only moderately elevated at 14.8 mU/L (N: 0-5.3; competitive radioimmunoassay, RIA), increased to 18.2 mU/L after thyrotropin-releasing hormone (TRH) stimulation, whereas prolactin increased normally. At age 15 years, after withdrawal of levothyroxine (LT4) therapy for 6 weeks, TRH stimulation slightly increased serum TSH using two immunometric assays, from less than 0.03 to 0.07 and from 0.2 to 0.3 (a monoclonal and polyclonal antibody), and from 1.9 to 4.1 mU/L using a polyclonal TSH antibody and iodinated recombinant TSH. Sequencing of the TSH-beta subunit gene revealed a homozygous single nucleotide deletion in codon 105 producing a frame shift that results in a truncated TSH-beta with nonhomologous 9 carboxyterminal amino acids and a loss of the 5 terminal residues. This mutation was previously reported in one Brazilian and two German families. The abnormal, and presumably biologically inactive, TSH can be detected in serum using appropriate antibodies. Its relatively small amount in serum is due to either reduced secretion or rapid degradation. The occurrence of the same mutation in three families of different ethnic origin suggests that this mutation may be prevalent in the population. Common ancestry or de novo mutations in a hot spot cannot be excluded. Finally, we must be aware that neonatal screening of congenital hypothyroidism based on blood spot TSH measurement will not detect this rare but severe genetic defect. |
| Databáze: | OpenAIRE |
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