engleski

Resistance to thyroid hormone in two generations with de-novo mutation traced to a mutation in ancestral germline - report of the first Croatian family

Introduction: Resistance to thyroid hormone (RTH) is primarily dominantly inherited and characterized by reduced organ responsiveness to thyroid hormone with elevated serum iodothyronines and unsuppressed TSH levels. It is most frequently caused by thyroid hormone receptor beta (THRB) gene mutations. We report a child and her mother with de-novo missense mutation in the THRB gene (H435Y) traced to a mutation in ancestral germline. Case study: A 7.5-yr-old girl presented with goiter. Parents report nervousness poor weight gain despite good appetite and occasional palpitations. Her weight was 24.9 kg (50 c.), height 138.3 cm (>95 c), heart rate 81/min, palpable goiter and warm and wet skin. Serum iodothyronines were elevated with a normal TSH suggesting RTH (Figure 1). There was perceptive hearing loss at 30dB. Her mother presented at age 12 years with symptoms of hyperthyroidism ; paroxysmal supraventricular tachycardia and goiter. Diagnosis of Graves’ disease, despite unsuppressed TSH suggesting RTH, led to antithyroid drug treatment, followed by thyroidectomy at the age of 14 years and subsequently levothyroxine therapy. Sequencing of the THRB gene revealed a single nucleotide substitution producing the missense mutation H435Y in both proband and her mother. Genotyping of the maternal grand parents revealed that the mutation in the mother originated de-novo in the THRB allele inherited from the maternal grand mother (Figure 1). Conclusion: We present the occurrence of RTH in two generations caused by THRB H435Y traced to a de-novo mutation in an ancestral allele. To our knowledge this is the first report of a THRB gene mutation in Croatia.

resistance to thyroid hormones, THRB gene mutation, germline mutation

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