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Cited by 78Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentHead and Neck Anomalies

Compound Heterozygous Mutations in the Thyroglobulin Gene (1143delC and 6725G→A [R2223H]) Resulting in Fetal Goitrous Hypothyroidism

Caron, Philippe, Moya, Christian M., Malet, David, Gutnisky, Viviana J., Chabardes, Bernard, Rivolta, Carina M., Targovnik, Héctor M.·2003·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2002-021744
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Abstract

In a 22-yr-old healthy woman, a fetal goiter was diagnosed coincidentally by ultrasound during the sixth month of gestation, and hypothyroidism was affirmed by a high TSH (336 mU/liter) concentration after cordocentesis. A second ultrasound examination at 27 wk gestation showed further enlargement of the goiter (34/21 mm). Two intraamniotic injections of 200 microg levothyroxine were performed during the seventh month of pregnancy. Ultrasound studies revealed a fetal goiter size of 30/18 mm during the eighth month of gestation. The woman delivered at term a female infant with an Apgar score of 10 at 1 and 5 min. Cord blood analysis indicated elevated TSH (284 mU/liter) and low free T(4) (5.5 pmol/liter) levels. The serum thyroglobulin (Tg) concentration was low (0.8 ng/ml), whereas ultrasound of the neonate indicated an enlarged thyroid gland (32/15/14 mm). During the second pregnancy, ultrasound examination revealed a goiter, and fetal hypothyroidism was also confirmed after umbilical vein blood sampling (TSH, 472 mU/liter). After two intraamniotic injections of 500 microg levothyroxine, the woman delivered a male infant at 37 wk of pregnancy. In cord blood the serum TSH concentration was 39 mU/liter, and the serum Tg level was low (0.7 ng/ml). The parents were nonconsanguineous. After birth of the two affected siblings, genomic DNA sequencing identified the presence of compound heterozygous mutations of the Tg gene: the paternal mutation consists of a cytosine deletion at nucleotide 1143 in exon 9 (1143delC), resulting in a frameshift that generates a stop codon at position 382, and the maternal mutation is a guanine to adenine substitution at position 6725 in exon 38, creating the R2223H missense mutation in the acetylcholinesterase homology domain of Tg. In conclusion, we report two siblings with congenital goiter and hypothyroidism caused by compound heterozygous mutations of the Tg gene.

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  • Genetic mutations of thyroid-specific proteins play a role in the development of fetal goiters.

    “Genetic mutations of thyroid-specific proteins also play a role in the development of fetal goiters (249–251).”

    From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [249]

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Authors
Caron, P., Moya, C. M., Malet, D., Gutnisky, V. J., Chabardes, B., Rivolta, C. M., & Targovnik, H. M.
Affiliations
  • Hôpital Rangueil (FR)
  • Universidad de Buenos Aires (AR)
Corresponding author
Targovnik, Héctor M.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2003-08
Volume
88
Issue
8
Pages
3546-3553
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2002-021744
OpenAlex
W2087510854
Cited by
78
References
51
Citations by year
2025: 1 · 2024: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 5
FWCI
4.07
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Head and Neck Anomalies
Keywords
thyroglobulin gene, congenital goiter, fetal hypothyroidism, familial hypothyroidism, siblings, pregnancy complications, TSH elevation
MeSH terms
Adult, Amino Acid Sequence, Base Sequence, DNA, Exons, Female, Goiter, Humans, Hypothyroidism, Molecular Sequence Data, Mutation, Pedigree, Thyroglobulin, Thyroid Function Tests, Ultrasonography, Frameshift Mutation, Sequence Deletion, Mutation, Missense, Reverse Transcriptase Polymerase Chain Reaction

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