The coexistence of mutations in the dual oxidase maturation factor 2 (DUOXA2) and dual oxidase 2 (DUOX2) genes is rarely identified in congenital hypothyroidism (CH). This study reports a boy with CH due to a novel splice-site mutation in the DUOXA2 gene and a missense mutation in the DUOX2 gene. A four-year-old boy was diagnosed with CH at neonatal screening and was enrolled in this study. The DUOXA2, DUOX2, thyroid peroxidase (TPO), and thyrotropin receptor (TSHR) genes were considered for genetic defects screening. Genomic DNA was extracted from peripheral blood leukocytes, and Sanger sequencing was used to screen the mutations in the exon fragments. Family members of the patient and the controls were also enrolled and evaluated. The boy harbored compound heterozygous mutations including a novel splice-site mutation c.554+5C>T in the maternal DUOXA2 allele and c.2654G>A (p.R885Q) in the paternal DUOX2 allele. The germline mutations from his parents were consistent with an autosomal recessive inheritance pattern. No mutations in the TPO and TSHR genes were detected. A novel splice-site mutation c.554+5C>T in the DUOXA2 gene and a mutation p.R885Q in the DUOX2 gene were identified in a 4-year-old patient with goitrous CH.

The mutations in the dual oxidase 2 (DUOX2) and dual oxidase maturation factor 2 (DUOXA2) genes can cause congenital hypothyroidism (CH). This study reports the pedigree with goitrous congenital hypothyroidism (GCH) due to the coexistence of heterozygous mutations in the DUOX2 and DUOXA2 genes. The two sisters with GCH were diagnosed with CH at neonatal screening and were enrolled in this study. The DUOX2, DUOXA2, and thyroid peroxidase (TPO) genes were considered for genetic defects screening. Family members of the patients and normal controls were also enrolled and evaluated. The two girls harbored compound heterozygous mutations, including a new mutation of c.2654G>T (p.R885L) in the maternal DUOX2 allele and c.738C>G (p.Y246X) in the paternal DUOXA2 allele, that has been previously reported. The germline mutations from the families were consistent with an autosomal recessive inheritance pattern. No mutations in the TPO gene and the controls were observed.