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Low levels of triiodothyronine (T3) in the brain lead to increased dopamine receptor sensitivity, potentially resulting in schizophrenia. Iodothyronine deiodinase 2 (DIO2) is the only enzyme which converts tetraiodothyronine (T4) to T3 in the brain. DIO2 polymorphism of rs225014 results in the expression of non-functioning DIO2. Therefore, this study aimed to investigate the association of rs255014 with schizophrenia and its impact on thyroid hormone levels. This study included 150 schizophrenia cases and 150 controls. DNA was extracted from blood and subjected to PCR and amplicon sequencing. Serum thyroid profiles were determined using chemiluminescent magnetic microparticle immunoassay. Statistical analyses involved independent sample t-tests, Chi-square, and Pearson's correlation tests. The results revealed a higher frequency of the reference genotype (TT) in controls compared to cases ( p < 0.05). However, rs225014 did not influence serum thyroid levels or the severity of schizophrenia ( p > 0.05). Interestingly, control subjects exhibited significantly higher T3 levels ( p < 0.001) than cases. Regardless of the genotype (TT or CC), the control group had higher mean T3 levels than the corresponding case group ( p < 0.05). In conclusion, rs225014 is associated with schizophrenia and has no effect on serum thyroid hormone levels.

Objective: In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH)., Context: Thyroid dyshormonogenesis comprises 10-15% of all cases of congenital hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease., Design: As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi-case families., Patients: One hundred and four patients with congenital TDH all coming from consanguineous and/or multi-case families., Measurements: Initially, we performed potential linkage analysis of cases to all seven causative-TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out., Results: TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N)., Conclusions: This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases., (© 2012 John Wiley & Sons Ltd.)

Backgrounds and Aims: Next generation sequencing (NGS) approaches have revolutionized the identification of mutations underlying genetic disorders. This technology is particularly useful for the identification of mutations in known and new genes for conditions with extensive genetic heterogeneity. In the present study we investigated a consanguineous Pakistani family with intellectual disability (ID)., Methods: Genotyping was carried out using 250k and 6k SNP microarrays in order to perform homozygosity mapping and copy number variation (CNV) analysis. Targeted NGS was performed to identify the genetic defect in this family. qPCR was performed to validate and confirm the NGS result., Results: Homozygosity mapping positioned the causative defect on chromosome 2p25.3-p25.2. Subsequent targeted NGS revealed an intragenic deletion of five exons of the gene TPO., Conclusions: NGS is a powerful method to uncover submicroscopic structural variations. This result demonstrates that an unbiased screening approach such as NGS can help to identify even unexpected disease-causing mutations., (Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.)