A novel compound heterozygous mutation in the thyroglobulin gene resulting in congenital goitrous hypothyroidism with high serum triiodothyronine levels.
Thyroglobulin abnormality is a rare cause of congenital hypothyroidism and only a limited number of mutations in the thyroglobulin gene have been reported. We analyzed the thyroglobulin gene in a patient with congenital goitrous hypothyroidism. This girl was identified with hyperthyrotropinemia in a neonatal mass-screening test. The patient had goiter, and her body weight gain was poor. Distal femoral epiphysis was absent on roentgenography. Her serum thyroxine level was low; however, her triiodothyronine level was high. Autoantibodies against triiodothyronine, thyroid peroxidase, and thyroglobulin were all negative. Her serum thyroglobulin level was undetectable. The thyroglobulin gene from the genomic DNA of the patient was analyzed by direct sequencing. Two novel heterozygous missense mutations, Cys1897Tyr (exon 31) and Arg2336Gln (exon 40), were found in the patient. The former mutation was derived from her mother, suggesting a compound heterozygous state. Normal triiodothyronine and low thyroxine concentrations are often observed in patients with thyroglobulin gene mutations. We considered that some patients with thyroglobulin abnormality might have high triiodothyronine levels. In cases of congenital goitrous hypothyroidism with normal-to-high triiodothyronine levels and low serum thyroglobulin levels, thyroglobulin abnormality should be considered.
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. sachi-tky@umin.ac.jp.|Department of Pediatrics, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan. sachi-tky@umin.ac.jp.
Sachiko
S
Kitanaka
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Ayaka
A
Takeda
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Utako
U
Sato
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yuko
Y
Miki
Department of Clinical Laboratory Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Akira
A
Hishinuma
Department of Clinical Laboratory Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Tamio
T
Ieiri
Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Takashi
T
Igarashi
D019943:Amino Acid Substitution; D003062:Codon; D003409:Congenital Hypothyroidism / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005973:Glutamine / Q000378:metabolism; D006042:Goiter / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013954:Thyroglobulin / Q000032:analysis / Q000235:genetics*; D013960:Thyroid Function Tests; D013974:Thyroxine / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000097:blood*
D003062:Codon; D014284:Triiodothyronine; D005973:Glutamine; D013954:Thyroglobulin; D013974:Thyroxine