Objectives: The c.2268dup mutation in the thyroid peroxidase (TPO) gene is the most common TPO alteration reported in Taiwanese patients with thyroid dyshormonogenesis. The ancestors of these patients are believed to originate from the southern province of China. Our previous study showed that this mutation leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in a Malaysian-Chinese family with goitrous hypothyroidism. The aim of our study was to provide further data on the incidence of the c.2268dup mutation in a cohort of Malaysian-Chinese and its possible phenotypic effects. Setting: Cohort study. Participants: Twelve biologically unrelated Malaysian-Chinese patients with congenital hypothyroidism were recruited in this study. All patients showed high TSH and low fT4 levels at the time of diagnosis with proven presence of thyroid gland Primary outcome measure: Screening of the c.2268dup mutation in the TPO gene in all patients was carried out using PCR-direct DNA sequencing method. Secondary outcome measure: Further screening for mutations in other exonic regions of the TPO gene was carried out if the patient is a carrier for the c.2268dup mutation Results: The c.2268dup mutation was detected in 4 out of the 12 patients. Apart from the c.2268dup and a previously documented mutation, c.2647C>T, two novel TPO alterations namely c.670_672del and c.1186C>T were also detected in our patients. In silico analyses predicted that the novel alteration affect the structure/function of the TPO protein. Conclusion: The c.2268dup was detected in approximately one third of the Malaysian-Chinese with thyroid dyshormonogenesis. The detection of the novel c.670_672del and c.1186C>T alterations expand the mutation spectrum of TPO associated with thyroid dyshormonogenesis.

Forward sequence (c.670_672 del)Chromatogram profile - Forward sequence (c.670_672 del)Forward.ab1Forward sequence (c.670_672del)FASTA sequence file - Forward sequence (c.670_672del)Forward.seqReverse sequence (c.670_672del)Chromatogram profile - Reverse sequence (c.670_672del)Reverse.ab1Reverse sequence (c.670_672del)FASTA sequence format - Reverse sequence (c.670_672del)Reverse.seqForward sequence (c.1186CT)Chromatogram - Forward sequence (c.1186CT)Forward.ab1Forward sequence (c.1186CT)FASTA format - Forward sequence (c.1186CT)Forward.seqReverse sequence (c.1186CT)Chromatogram - Reverse sequence (c.1186CT)Reverse.ab1Reverse sequence (c.1186CT)FASTA format - Reverse sequence (c.1186CT)Reverse.seqwt-lowest-energy-structureWild-type pdb file to be opened/viewed using Accelrys Discovery Studio or DeepView-Swiss Pdb ViewerASP224-md-10nsASP224-md-10ns pdb file to be opened/viewed using Accelrys Discovery Studio or DeepView-Swiss Pdb ViewerARG396-md-10nsARG396-md-10ns file to be opened/viewed using Accelrys Discovery Studio or DeepView-Swiss Pdb Viewer