Detection of Novel Gene Variants Associated with Congenital Hypothyroidism in a Finnish Patient Cohort
| Autor: | Marja Ojaniemi, Teemu Kuulasmaa, Jukka Kero, Krista Rantakari, Jaakko Ignatius, Juha-Pekka Pursiheimo, Jorma Toppari, Christoffer Löf, Henriette Undeutsch, Jarmo Jääskeläinen, Markku Laakso, Konrad Patyra, Heike Biebermann, Tuulia Pajunen, Gunnar Kleinau, Taina Mustila, Heiko Krude, Jagadish Vangipurapu, Andreina Kero, Päivi J. Miettinen, Turkka Kirjavainen, Peter Kühnen, Holger Jaeschke |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Candidate gene Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Disease ta3111 medicine.disease_cause Autoantigens Iodide Peroxidase Cohort Studies 03 medical and health sciences Exon PAX8 Transcription Factor 0302 clinical medicine Endocrinology Iron-Binding Proteins medicine Congenital Hypothyroidism Humans Genetic Testing Gene Finland Genetic testing Genetics Mutation medicine.diagnostic_test business.industry Infant Newborn Original StudiesThyroid Dysfunction: Hypothyroidism Thyrotoxicosis and Thyroid Function Tests Receptors Thyrotropin medicine.disease ta3123 Congenital hypothyroidism Pedigree 030104 developmental biology Female PAX8 business |
| Zdroj: | Thyroid |
| ISSN: | 1557-9077 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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