A novel homozygous missense mutation of the dual oxidase 2 (DUOX2) gene in an adult patient with large goiter.
OBJECTIVE
To describe the first adult case of large goiter associated with a novel R1110Q mutation in the dual oxidase 2 (DUOX2) gene. She was initially euthyroid, and developed hypothyroidism later in her forties. DUOX2 is an essential enzyme in iodine organification of thyroid hormone biosynthesis. Only infant cases of congenital hypothyroidism due to mutations of the DUOX2 gene have been reported. Biallelic mutation of DUOX2 is thought to lead to total iodine organification defect. PATIENTS AND MEASUREMENT: This 57-year-old woman became first aware of goiter around the age of 20 years. Since the goiter had enlarged gradually, she consulted us at the age of 32 years. Goiter was soft, and thyroid function was normal. Antithyroid antibodies were negative. Both physical and mental development was normal. Three of her nine siblings and her mother had large goiters. At the age of 44 years, thyroid function demonstrated subclinical hypothyroidism. She started to take levo-thyroxine at a dose of 100 mug/day to reduce goiter. At the age of 56 years, goiter size remained the same. The perchlorate discharge rate was 72.8%, suggesting partial iodine organification defect. Thus, thyroid peroxidase (TPO) gene and DUOX2 gene were analyzed.


RESULTS
There was no mutation in the TPO gene, but a novel homozygous mutation (R1110Q) in the DUOX2 gene was identified. The same heterozygous mutation was detected in her two sons and two grandchildren. This mutation was not detected in 104 control alleles and was located at a site differing from any other reported mutations in the DUOX2 gene.


CONCLUSIONS
This homozygous missense mutation can be associated with thyroid dysfunction and goiter formation of an enlarged thyroid gland.
Ohye
Hidemi
H
Department of Internal Medicine, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe, Japan. ohye@kuma-h.or.jp
Fukata
Shuji
S
Hishinuma
Akira
A
Kudo
Takumi
T
Nishihara
Eijun
E
Ito
Mitsuru
M
Kubota
Sumihisa
S
Amino
Nobuyuki
N
Ieiri
Tamio
T
Kuma
Kanji
K
Miyauchi
Akira
A
D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D002675:Child, Preschool; D000074623:Dual Oxidases; D005260:Female; D006042:Goiter / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D019255:NADPH Oxidases / Q000032:analysis / Q000235:genetics*; D010375:Pedigree; D013974:Thyroxine / Q000627:therapeutic use
D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human; D013974:Thyroxine