Monogenic Hashimoto thyroiditis associated with a variant in the thyroglobulin (TG) gene.

Abstract

BACKGROUND:

Risk of autoimmune thyroid disease (AITD) is strongly heritable. Multiple genes confer increased risk for AITD, but a monogenic origin has not yet been described. We studied a family with apparent autosomal dominant, early onset Hashimoto thyroiditis.

METHODS:

The family was enrolled in an IRB-approved protocol. Whole exome sequencing was used to study the proband and an affected sibling. The identified variant was studied in other family members by Sanger sequencing.

RESULTS:

We identified a previously unreported splice site variant in the thyroglobulin gene (TG c.1076-1G > C). This variant was confirmed in all affected family members who underwent testing, and also noted in one unaffected child. The variant is associated with exon 9 skipping, resulting in a novel in-frame variant transcript of TG.

CONCLUSION:

We discovered a monogenic form of AITD associated with a splice site variant in the thyroglobulin gene. This finding raises questions about the origins of thyroid autoimmunity; possible explanations include increased immunogenicity of the mutated protein or thyroid toxicity with secondary development of anti-thyroid antibodies. Further study into the effects of this variant on thyroid function and thyroid autoimmunity are warranted.

• Authors: Mindy S Lo, Meghan Towne, Grace E VanNoy, Catherine A Brownstein, Andrew A Lane, Talal A Chatila, Pankaj B Agrawal
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 86 Pg. 116-119 (01 2018) ISSN: 1095-9157 [Electronic] England
• PMID: 28942902 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Autoantibodies
• Milk Proteins
• Monogen
• RNA Isoforms
• Thyroglobulin

Topics

• Adolescent
• Adult
• Aged
• Autoantibodies (metabolism)
• Cells, Cultured
• Child
• Chromosome Disorders
• Female
• Genetic Association Studies
• Hashimoto Disease (genetics)
• Humans
• Male
• Middle Aged
• Milk Proteins (genetics)
• Mutation (genetics)
• Pedigree
• Polymorphism, Genetic
• RNA Isoforms (genetics)
• T-Lymphocytes (immunology)
• Thyroglobulin (genetics)
• Exome Sequencing
• Young Adult