Dumitrescu et al. (2005) described 2 families with a specific thyroid phenotype associated with a reduction in type II iodothyronine deiodinase (DIO2; 601413) activity. In a Bedouin Saudi family, 3 of 7 sibs had abnormal thyroid function tests. ... Dumitrescu et al. (2005) described 2 families with a specific thyroid phenotype associated with a reduction in type II iodothyronine deiodinase (DIO2; 601413) activity. In a Bedouin Saudi family, 3 of 7 sibs had abnormal thyroid function tests. The proband had short stature at 14 years of age and delayed bone age of 9 at 12 years of age, while still prepubertal. During the ensuing 2 years, a pubertal growth spurt brought his height to normal. At neonatal screening his blood thyrotropin (TSH; see 188540) level was high, but no treatment was given because serum thyroxine (T4) was not low. TSH levels remained above normal, but development proceeded normally. Concentrations of total T4, free T4, and total triiodothyronine metabolite (reverse T3) were high, whereas those of total and free T3 were low. The same pattern of thyroid function test abnormalities was observed in the proband's 7-year-old brother and 4-year-old sister, both clinically euthyroid. All other family members had normal thyroid function tests. Fibroblasts from the 3 sibs showed decreased DIO2 enzymatic activity not linked to the DIO2 locus. The single affected child of an Irish family presented at age 6 with transient growth retardation and thyroid abnormalities similar to those observed in affected members of the Bedouin Saudi family.
Dumitrescu et al. (2005) performed systematic linkage analysis of genes involved in DIO2 synthesis and degradation and identified mutations in the SECISBP2 gene as the cause of the disorder. The Bedouin family carried a homozygous missense mutation in ... Dumitrescu et al. (2005) performed systematic linkage analysis of genes involved in DIO2 synthesis and degradation and identified mutations in the SECISBP2 gene as the cause of the disorder. The Bedouin family carried a homozygous missense mutation in exon 12 resulting in the amino acid substitution arg540-to-gln (607693.0001). The proband of the Irish family was compound heterozygous for a nonsense mutation in exon 10 and a splice mutation at the intron 8 splice donor site (see 607693.0002). Because SECISBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Dumitrescu et al. (2005) hypothesized that incomplete loss of SECISBP2 function probably caused the mild phenotype.