Mutations in proteasome-related genes are associated with thyroid hemiagenesis
| Autor: | Witold Szaflarski, Ewelina Szczepanek-Parulska, Kosma Woliński, Katarzyna Ziemnicka, Katarzyna Piatek, Luiza Handschuh, Marek Figlerowicz, Joanna Wesoly, Bartłomiej Budny, Marek Niedziela, Maciej Zabel, Tomasz Zemojtel, Marek Ruchała, Małgorzata Rydzanicz |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Exome sequencing Pathology medicine.medical_specialty endocrine system Proteasome Endopeptidase Complex Microarray endocrine system diseases Thyroid hemiagenesis Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Biology Bioinformatics 03 medical and health sciences 0302 clinical medicine Endocrinology Gene Duplication medicine Thyroid transcription factors Humans Genetic Predisposition to Disease Endocrine Genetics/Epigenetics Gene Genetic Association Studies Proteasome Thyroid TNF Receptor-Associated Factor 2 030104 developmental biology medicine.anatomical_structure Mutation Thyroid Dysgenesis Etiology Human thyroid Gene Deletion |
| Zdroj: | Endocrine |
| ISSN: | 1559-0100 1355-008X |
| Popis: | Purpose Human thyroid development is a complex and still unexplained process. Thyroid hemiagenesis is a congenital anomaly, where one of the thyroid lobes fails to develop. In the majority of patients with thyroid hemiagenesis, the genetic background remains unknown. The aim of the study was to search for novel genetic contributors to the etiology of thyroid hemiagenesis. Methods A cohort of 34 sporadic patients diagnosed with thyroid hemiagenesis and one three-generation family were subjected to comprehensive genomic examination. Initially, targeted screening of associated transcription factors, known to be linked to thyroid development, was performed. As a next step, genomic examinations were applied using high-resolution microarrays, whereas for the thyroid hemiagenesis family, additionally the whole exome sequencing was performed. Results Screening of transcription factors revealed no causative mutations in the studied cohort. Genomic examinations revealed the presence of four recurrent defects (three deletions and one duplication) affecting highly conservative proteasome genes PSMA1, PSMA3, and PSMD3. In a thyroid hemiagenesis family a splice site mutation in a proteasome gene PSMD2 (c.612T > C cDNA.1170T > C, g.3271T > C) was found in both affected mother and daughter. Conclusions Our results shed a new light on etiology of thyroid hemiagenesis, so far suspected to be linked only to mutations in the genes directly involved in the thyroid development. We demonstrated, for the first time, that genomic alterations in proteasome-associated genes co-occur in patients presenting this developmental anomaly. |
| Databáze: | OpenAIRE |
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