A 5-year-old male with growth retardation and mild intellectual impairment has an enlarged thyroid. His serum thyroid-stimulating hormone (TSH) level is 4.3 mU/L (normal: 0.1-4.0 mU/L), and his serum thyroglobulin level is <15 pmol/L (normal: 15-50 pmol/L). A biopsy of the thyroid stained with antithyroglobulin antibodies reveals accumulation of thyroglobulin in the rough endoplasmic reticulum. Which of the following underlying defects is most likely in this male?

1. A)Loss of function mutation in the DNA encoding the hydrophobic signal sequence on thyroglobulin
2. B)Loss of function mutation in the ubiquitin gene
3. C)Thyroglobulin monomer misfolding and failure of subunit assemblyGABARITO
4. D)Failure to phosphorylate mannose attached to thyroglobulin
5. E)A TSH receptor defect