TY - JOUR
T1 - A Novel Mutation in the Thyroglobulin Gene Resulting in Neonatal Goiter and Congenital Hypothyroidism in an Eritrean Infant
AU - Stern, Eve
AU - Schoenmakers, Nadia
AU - Nicholas, Adeline K.
AU - Kassif, Eran
AU - Hamiel, Orit Pinhas
AU - Yeshayahu, Yonatan
N1 - Publisher Copyright:
© 2022 by Turkish Society for Pediatric Endocrinology and Diabetes.
PY - 2022
Y1 - 2022
N2 - Congenital hypothyroidism (CH) due to dyshormonogenesis may occur due to mutations in any of the key genes involved in thyroid hormone biosynthesis (TG, TPO, DUOX2, DUOXA2, SLC5A5, IYD, SLC26A4 and SLC26A7). Mutations in the thyroglobulin gene (TG) are frequently associated with goiter, which may present fetally or neonatally, although a spectrum of phenotypes is reported. We present the case of a woman of Eritrean origin who presented in the third trimester of pregnancy in the early stages of labor. Ultrasound at presentation revealed a fetal neck swelling consistent with a goiter. Following delivery by Caesarian section with minimal respiratory support, the infant was found to be hypothyroid with undetectable serum levels of thyroglobulin. Sequencing of the TG revealed a homozygous donor splice site pathogenic variant (c.5686+1delG) not previously described in the literature. Levothyroxine treatment resulted in normal growth and psychomotor development. Goitrous CH with inappropriately low thyroglobulin has previously been reported in patients harbouring homozygous single nucleotide substitutions at the same TG donor splice site, which result in exon skipping and retention of malformed thyroglobulin by the endoplasmic reticulum. We conclude that the TG c.5686+1delG pathogenic variant is the likely basis for our patient’s fetal goiter and CH, and that the clinical phenotype associated with TG c.5686+1delG is comparable to that seen with single nucleotide substitutions at the same site.
AB - Congenital hypothyroidism (CH) due to dyshormonogenesis may occur due to mutations in any of the key genes involved in thyroid hormone biosynthesis (TG, TPO, DUOX2, DUOXA2, SLC5A5, IYD, SLC26A4 and SLC26A7). Mutations in the thyroglobulin gene (TG) are frequently associated with goiter, which may present fetally or neonatally, although a spectrum of phenotypes is reported. We present the case of a woman of Eritrean origin who presented in the third trimester of pregnancy in the early stages of labor. Ultrasound at presentation revealed a fetal neck swelling consistent with a goiter. Following delivery by Caesarian section with minimal respiratory support, the infant was found to be hypothyroid with undetectable serum levels of thyroglobulin. Sequencing of the TG revealed a homozygous donor splice site pathogenic variant (c.5686+1delG) not previously described in the literature. Levothyroxine treatment resulted in normal growth and psychomotor development. Goitrous CH with inappropriately low thyroglobulin has previously been reported in patients harbouring homozygous single nucleotide substitutions at the same TG donor splice site, which result in exon skipping and retention of malformed thyroglobulin by the endoplasmic reticulum. We conclude that the TG c.5686+1delG pathogenic variant is the likely basis for our patient’s fetal goiter and CH, and that the clinical phenotype associated with TG c.5686+1delG is comparable to that seen with single nucleotide substitutions at the same site.
KW - Congenital goiter
KW - case report
KW - hypothyroidism
KW - novel mutation
KW - thyroglobulin
UR - http://www.scopus.com/inward/record.url?scp=85109091478&partnerID=8YFLogxK
U2 - 10.4274/jcrpe.galenos.2021.2020.0278
DO - 10.4274/jcrpe.galenos.2021.2020.0278
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C2 - 33832185
AN - SCOPUS:85109091478
SN - 1308-5727
VL - 14
SP - 221
EP - 226
JO - JCRPE Journal of Clinical Research in Pediatric Endocrinology
JF - JCRPE Journal of Clinical Research in Pediatric Endocrinology
IS - 2
ER -