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TUBB1 mutations cause thyroid dysgenesis associated with abnormal platelet physiology
- Source :
- EMBO Molecular Medicine, EMBO Molecular Medicine, Wiley Open Access, 2018, ⟨10.15252/emmm.201809569⟩, EMBO Molecular Medicine, Vol 10, Iss 12, Pp n/a-n/a (2018)
- Publication Year :
- 2019
- Publisher :
- Bioscientifica, 2019.
-
Abstract
- The genetic causes of congenital hypothyroidism due to thyroid dysgenesis (TD) remain largely unknown. We identified three novel TUBB1 gene mutations that co‐segregated with TD in three distinct families leading to 1.1% of TUBB1 mutations in TD study cohort. TUBB1 (Tubulin, Beta 1 Class VI) encodes for a member of the β‐tubulin protein family. TUBB1 gene is expressed in the developing and adult thyroid in humans and mice. All three TUBB1 mutations lead to non‐functional α/β‐tubulin dimers that cannot be incorporated into microtubules. In mice, Tubb1 knock‐out disrupted microtubule integrity by preventing β1‐tubulin incorporation and impaired thyroid migration and thyroid hormone secretion. In addition, TUBB1 mutations caused the formation of macroplatelets and hyperaggregation of human platelets after stimulation by low doses of agonists. Our data highlight unexpected roles for β1‐tubulin in thyroid development and in platelet physiology. Finally, these findings expand the spectrum of the rare paediatric diseases related to mutations in tubulin‐coding genes and provide new insights into the genetic background and mechanisms involved in congenital hypothyroidism and thyroid dysgenesis.
- Subjects :
- 0301 basic medicine
Medicine (General)
Pathology
endocrine system diseases
Platelet Aggregation
[SDV]Life Sciences [q-bio]
Physiology
Gene mutation
QH426-470
Mice
TUBB1
Tubulin
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Research Articles
Mice, Knockout
Hematology
TUBB1 Subject Categories Genetics
Thyroid
congenital hypothyroidism
Congenital hypothyroidism
3. Good health
medicine.anatomical_structure
Thyroid Dysgenesis
Molecular Medicine
Research Article
Blood Platelets
endocrine system
medicine.medical_specialty
Protein family
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Gene Therapy & Genetic Disease
Thyroid dysgenesis
03 medical and health sciences
R5-920
Internal medicine
Genetics
[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
medicine
Animals
Humans
Gene
Abnormal Platelet
macroplatelets
business.industry
mutations
medicine.disease
030104 developmental biology
Mutation
Genetics, Gene Therapy & Genetic Disease
business
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Haematology
Subjects
Details
- ISSN :
- 16624009, 17574676, and 17574684
- Database :
- OpenAIRE
- Journal :
- Yearbook of Paediatric Endocrinology
- Accession number :
- edsair.doi.dedup.....b73de1dd5eb372bad9b8ac5c11150b02