Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community. (6th May 2013)

• Record Type: Journal Article
• Authors: Cangul, Hakan; Aycan, Zehra; Olivera‐Nappa, Alvaro; Saglam, Halil; Schoenmakers, Nadia A.; Boelaert, Kristien; Cetinkaya, Semra; Tarim, Omer; Bober, Ece; Darendeliler, Feyza; Bas, Veysel; Demir, Korcan; Aydin, Banu K.; Kendall, Michaela; Cole, Trevor; Högler, Wolfgang; Chatterjee, V. Krishna K.; Barrett, Timothy G.; Maher, Eamonn R.
• Is Part Of: Clinical endocrinology. Volume 79:Number 2(2013:Aug.)
• Page Start: 275
• Page End: 281
• Publication Date: 2013-05-06
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12127
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12127-abs-0001"> <title>Summary</title> <sec id="cen12127-sec-0001" sec-type="section"> <title>Objective</title> <p>In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH).</p> </sec> <sec id="cen12127-sec-0002" sec-type="section"> <title>Context</title> <p>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 (<italic>NIS, TPO, PDS, TG, IYD, DUOX2</italic> and <italic>DUOXA2</italic>) have been implicated in the aetiology of the disease.</p> </sec> <sec id="cen12127-sec-0003" sec-type="section"> <title>Design</title> <p>As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi‐case families.</p> </sec> <sec id="cen12127-sec-0004" sec-type="section"> <title>Patients</title> <p>One hundred and four patients with congenital TDH all coming from consanguineous and/or multi‐case families.</p> </sec> <sec id="cen12127-sec-0005" sec-type="section"> <title>Measurements</title> <p>Initially, we performed potential linkage analysis of cases to all seven causative‐TDH loci as well as direct sequencing of the <italic>TPO</italic> gene in cases we could not exclude linkage to this locus. In addition, <italic>in silico</italic> analyses of novel missense mutations were carried out.</p> </sec> <sec id="cen12127-sec-0006" sec-type="section"> <title>Results</title> <p> <italic>TPO</italic> had the highest potential for linkage and we identified 21 <italic>TPO</italic> mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct <italic>TPO</italic> mutations detected in this study were novel (A5T, Y55X, E596X, D633N).</p> </sec> <sec id="cen12127-sec-0007" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>