University of Oulu

Detection of Novel Gene Variants Associated with Congenital Hypothyroidism in a Finnish Patient Cohort, Löf Christoffer, Patyra Konrad, Kuulasmaa Teemu, Vangipurapu Jagadish, Undeutsch Henriette, Jaeschke Holger, Pajunen Tuulia, Kero Andreina, Krude Heiko, Biebermann Heike, Kleinau Gunnar, Kühnen Peter, Rantakari Krista, Miettinen Päivi, Kirjavainen Turkka, Pursiheimo Juha-Pekka, Mustila Taina, Jääskeläinen Jarmo, Ojaniemi Marja, Toppari Jorma, Ignatius Jaakko, Laakso Markku, and Kero Jukka, Thyroid 2016, 26 9, 1215 -1224

Detection of novel gene variants associated with congenital hypothyroidism in a Finnish patient cohort

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Author: Löf, Christoffer1; Patyra, Konrad1; Kuulasmaa, Teemu2;
Organizations: 1Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland
2Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
3Institute of Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Berlin, Germany
4Hospital for Children and Adolescents, Hospital District of Helsinki and Uusimaa, Helsinki, Finland
5Turku Clinical Sequencing Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
6Department of Pediatrics, Seinäjoki Central Hospital, Seinäjoki, Finland
7Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
8Department of Pediatrics, Turku University Hospital, Turku, Finland
9Department of Clinical Genetics, Turku University Hospital, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
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Language: English
Published: Mary Ann Liebert, 2016
Publish Date: 2017-02-06


Background: Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH.

Methods: A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH.

Results: Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro.

Conclusion: In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH.

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Series: Thyroid
ISSN: 1050-7256
ISSN-E: 1557-9077
ISSN-L: 1050-7256
Volume: 26
Issue: 9
Pages: 1215 - 1224
DOI: 10.1089/thy.2016.0016
Type of Publication: A1 Journal article – refereed
Field of Science: 1184 Genetics, developmental biology, physiology
3111 Biomedicine
3123 Gynaecology and paediatrics
Funding: The study was supported by the Finnish Cultural Foundation (C.L.), Medicinska Understödsföreningen Liv & Hälsa r.f (C.L.), Finnish Academy of Science (J.K.), Finnish Pediatric and Medical Foundations (J.K.), EVO grant from Turku University Hospital, and The Finnish Medical Foundation (J.K.).
Copyright information: ©Christoffer Lo¨f et al. 2016; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( which permits any noncom- mercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.