Resistance to thyroid hormone in a family with no TRbeta gene anomaly: pathogenic hypotheses.
Syndromes of resistance to thyroid hormone (RTH) are almost always linked to a defective triiodothyronine-receptor B gene (TRB). Only six families with RTH exhibiting a normal TRB gene have been reported so far. We report another and discuss possible mechanisms.


METHODS
We studied a kindred expressing a typical RTH phenotype. DNA was amplified and the TRB gene was sequenced. Linkage analysis assessed linkage between the TRB gene and RTH phenotype.


RESULTS
Direct sequencing of the TRB gene failed to identify any anomaly in the coding exons. Linkage analysis demonstrated that the RTH phenotype was not linked to the TRB gene in this family.


CONCLUSIONS
TRB1 and TRB2 genes were not defective in this family. Multiple mechanisms might account for this situation at the pre-receptor, receptor and post-receptor levels. The most likely hypothesis is the involvement of an abnormal nuclear cofactor serving a specific function in the regulation of thyroid hormone action.
Vlaeminck-Guillem
V
V
Clinique Endocrinologique Marc Linquette, USNA, CHRU de Lille 6, rue du Pr Laguesse, France.
Margotat
A
A
Torresani
J
J
D'herbomez
M
M
Decoulx
M
M
Wémeau
J L
JL
D000328:Adult; D018900:Dinucleotide Repeats; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013974:Thyroxine