Resistance to Thyroid Hormone: Probable De Novo Mutation (P453S) in the Receptor Beta Gene - Original Article

Abstract
Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced sensitivity to thyroid hormone (TH), usually due to mutations in the thyroid hormone receptor (TR) b gene. We studied a Turkish family whose proband, a 19-year-old male, presented with diffuse goiter, nervousness, and palpitation. Thyroid function tests revealed elevated levels of TH and nonsuppressed thyrotropin (TSH). Gene sequencing revealed a mutation in one allele of the TRb gene in the proband, his two brothers, and father. It involved the substitution of the normal cytosine 1642 with a thymidine, resulting in the replacement of the normal proline 453 with a serine (P453S) in the T3-binding domain of the TRb  which is known to have one quarter to one third the T3-binding affinity of the normal TRb Genetic study of the family suggests that the mutation may have occurred de-novo in the father of the proband.