Identification and functional studies of two new dual-oxidase 2 (DUOX2) mutations in a child with congenital hypothyroidism and a eutopic normal-size thyroid gland.
BACKGROUND
Some cases of congenital hypothyroidism (CH) are associated with a gland of normal size.


OBJECTIVE
To explore the cause of organification defect in one child with CH and a eutopic thyroid gland, genetic analyses of TPO, DUOX2, and DUOXA2 genes were performed.


METHODS
One child with CH, a eutopic thyroid gland, and a partial organification defect was shown after (123)I scintigraphy and perchlorate test.


METHODS
In the child with the organification defect, TPO, DUOX2, and DUOXA2 genes were analyzed. The functional activity of the DUOX2 mutants was studied after expression in eukaryotic cells.


RESULTS
No TPO or DUOXA2 gene mutations were identified. Direct sequencing of the DUOX2 gene revealed a compound heterozygous genotype for S911L and C1052Y substitutions. S911L and C1052Y caused a partial defect in H(2)O(2) production after transient expression in HeLa cells.


CONCLUSIONS
We performed a genetic analysis in one child with CH and a eutopic thyroid gland. Two new mutations in DUOX2 gene responsible for the partial deficit in the organification process were identified.
Tonacchera
Massimo
M
Dipartimento di Endocrinologia e Metabolismo, Centro Eccellenza AmbiSEN, Università di Pisa, 56124 Pisa, Italy. mtonacchera@hotmail.com
De Marco
Giuseppina
G
Agretti
Patrizia
P
Montanelli
Lucia
L
Di Cosmo
Caterina
C
Freitas Ferreira
Andrea Claudia
AC
Dimida
Antonio
A
Ferrarini
Eleonora
E
Ramos
Helton Estrela
HE
Ceccarelli
Claudia
C
Brozzi
Federica
F
Pinchera
Aldo
A
Vitti
Paolo
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001724:Birth Weight; D002585:Cesarean Section; D002648:Child; D000013:Congenital Abnormalities / Q000235:genetics; D000074623:Dual Oxidases; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007457:Iodine Radioisotopes; D007565:Jaundice / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics*; D011247:Pregnancy; D011877:Radionuclide Imaging; D012016:Reference Values; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D007457:Iodine Radioisotopes; D013972:Thyrotropin; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human; D013974:Thyroxine