Prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis.
OBJECTIVE
To ascertain the prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis (JT) in non-autoimmune patients. TSH receptor gene mutations are not seen in autoimmune-active patients.


METHODS
In a nationwide study on JT, 123 patients were re-examined 10 y (range 4 to 21 y) after diagnosis. Two patients with toxic adenoma were excluded. In 25 patients, no TPO, TG or TSH-R antibodies were found. In 17 patients, DNA material was available for TSH receptor gene analysis. The entire TSH receptor gene was sequenced in five patients. TSH receptor "hot spots" for mutations in exon 9 and 10 were sequenced in the remaining 12 patients.


RESULTS
A TSH receptor gene germline mutation was identified in only one patient of a total number of 121 patients with JT, of which 17 patients were presumed to have non-autoimmune JT by the lack of thyroid autoantibodies.


CONCLUSIONS
In Denmark the prevalence of germline mutations in the TSH receptor gene is one in 121 patients with JT (0.8%; 95% CI: 0.02-4.6%) and one in 17 patients with presumed non-autoimmune JT (6%; 95% CI: 5.88% (0.15-28.69)).
Lavard
L
L
Department of Paediatrics, Glostrup Hospital, Glostrup, Denmark. lenl@glostruphosp.kbhamt.dk
Jacobsen
B Brock
BB
Perrild
H
H
Vassart
G
G
Parma
J
J
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005091:Exons / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood; D015995:Prevalence; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013971:Thyrotoxicosis / Q000453:epidemiology / Q000235:genetics*
D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin