Genetics and Hashimoto thyroiditis - Two papers

It has always looked to me as if there is a genetic component to thyroid disease - and specifically to Hashimoto's. Now not one, but two papers...

J Autoimmun. 2017 Sep 21. pii: S0896-8411(17)30528-0. doi: 10.1016/j.jaut.2017.09.003. [Epub ahead of print]

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

Lo MS1, Towne M2, VanNoy GE2, Brownstein CA2, Lane AA3, Chatila TA4, Agrawal PB5.

Author information

1 Divisions of Immunology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States. Electronic address: mindy.lo@childrens.harvard.edu.

2 Genetics and Genomics, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.

3 Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States.

4 Divisions of Immunology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States.

5 Genetics and Genomics, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States; Division of Newborn Medicine, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States.

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.

Copyright © 2017 Elsevier Ltd. All rights reserved.

PMID: 28942902

DOI: 10.1016/j.jaut.2017.09.003

ncbi.nlm.nih.gov/pubmed/289...

CLINICAL THYROIDOLOGY FOR THE PUBLIC

A publication of the American Thyroid Association

Summaries for the Public from recent articles in Clinical Thyroidology

HYPOTHYROIDISM

First-degree family members of patients with hypothyroidism due to Hashimoto’s Thyroiditis have an increased risk of developing hypothyroidism

BACKGROUND

The most common cause of hypothyroidism is Hashimoto’s thyroiditis. This is an autoimmune disease where the patient’s antibodies, which usually fight infection, get confused and attack the body. In the case of Hashimoto’s thyroiditis, the antibodies attack the thyroid and destroy it. As the disease progresses, the thyroid gland is unable to produce enough thyroid hormone and the patients develop hypothyroidism. Family members of patients with hypothyroidism due to Hashimoto’s thyroiditis have a higher risk to develop this disorder, but it is unclear what degree is this risk. The aim of this study was to evaluate the risk of developing the disease in firstdegree relatives (parents, children, siblings) of patients with hypothyroidism due to Hashimoto’s thyroiditis as compared with the general population in an Indian population.

More to read by following link below:

thyroid.org/patient-thyroid...

5 Replies

oldestnewest
  • helvella,

    It had to happen eventually as I believe is the way forward.

    Many are intrigued by the possibility that genetic testing may tell more about a person's future health "hazards". We already know how the DI02 genetic differences influence the effectiveness of thyroid hormone replacement and in the way individuals make T3 out of T4. I also had genetic testing to diagnosis Heamochromotosis.

    Viruses, bacterial infections, parasites, gluten, elevated oestrogen, low Vit D levels, intestinal permeability, environmental toxins (mercury//lead), as well as stress, etc .... have all been sighted for the reasoning of Hashimoto onset but for that to happen, surely we must have a genetic predisposition in the first instance.

    There are a number of ethical dilemmas involved in revealing one’s predisposition to certain disease/illness and of course the knowing is only useful if we are to act accordingly and give ourselves a better chance of avoidance or decreasing the severity by taking the necessary steps.

    Thank you for posting.

  • radd,

    Even without knowing which genes, simply accepting that there is a hereditary element would be a start!

    Since I first got into the thyroid world it has been obvious that there are genetic factors - but that they are often anything but simple. When people are told that thyroid issues in their family mean nothing, it is intensely annoying.

  • helvella,

    Although been around a while, it is a whole new field in the public eye and one fraught with problems.

    Used sensitively and with support it has to help long term .... although sadly it will take years and years before our common or garden family GP's (or endo's) realise the full implications of "thyroid issues in the family".

    But on a more positive note ....... discovery has to start somewhere ... :o)) ..

  • My late grandmother, my late mother, me and my daughter all had/have thyroid problems.

  • Me, my sister, my Grandmother and many family members on both sides of my family have or had this disease.

You may also like...