A new case of familial nonautoimmune hyperthyroidism caused by the M463V mutation in the TSH receptor with anticipation of the disease across generations: a possible role of iodine supplementation.
OBJECTIVE
Hereditary (familial) nonautoimmune hyperthyroidism (FNAH) is caused by activating thyroid-stimulating hormone (thyrotropin) receptor (TSHR) germline mutations. We describe a family with recurrent thyrotoxicosis and goiter across three generations, including an 8-year-old girl.


RESULTS
Sequences of the TSHR gene in the index patient, her father, her paternal grandmother, and a paternal uncle demonstrated the presence of an identical germline TSHR mutation. The mutation was heterozygous and determined the substitution of valine for methionine (codon 463; ATG-->GTG) in the second transmembrane domain of the TSHR in all the affected patients, but in none of the unaffected family members.


CONCLUSIONS
We compared the clinical presentation of FNAH in the family reported by us with the other cases harboring the same mutation reported in the literature. This analysis revealed high variability in the phenotypical expression of the disease. In the family reported by us, we also observed a clear anticipation of the onset of the disease across generations, and we discussed whether such a phenomenon can be the consequence of the increased iodine supplementation in the area where the family lives.
Ferrara
Alfonso Massimiliano
AM
Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università deglli Studi di Napoli Federico II, Napoli, Italy.
Capalbo
Donatella
D
Rossi
Giuseppina
G
Capuano
Serena
S
Del Prete
Giuseppina
G
Esposito
Valentina
V
Montesano
Giovanna
G
Zampella
Emilia
E
Fenzi
Gianfranco
G
Salerno
Mariacarolina
M
Macchia
Paolo Emidio
PE
D019943:Amino Acid Substitution; D002648:Child; D019587:Dietary Supplements; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy / Q000235:genetics*; D007455:Iodine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013610:Tachycardia / Q000209:etiology; D013960:Thyroid Function Tests; D014202:Tremor / Q000209:etiology
D011989:Receptors, Thyrotropin; D007455:Iodine