Detection of combined genomic variants in a Jordanian family with familial non-autoimmune hyperthyroidism

Abstract

Five patients, four brothers and their paternal aunt, presented with a history of overt hyperthyroidism and goiter. Hyperthyroidism in this family was remarkable for its poor response to carbimazole (30-50 mg/d). The thyroid ultrasound showed a diffusely enlarged gland in all the affected members, and thyroid stimulating antibodies (TSAB) were negative. Screening for germline mutations in thyroid stimulating hormone (TSH) receptor (TSHR) gene was performed by direct sequencing of genomic DNA extracted from peripheral blood leukocytes of all family members. The sequence analysis of all TSHR gene exons and intron borders revealed two genomic variants. The first was a single nucleotide polymorphism (SNP) within exon seven (Asn187Asn), whereas the other was located in intron seven (IVS7+68TG). All affected members, two asymptomatic brothers with sub-clinical hyperthyroidism, and their father were heterozygous for those two genomic variants. Anti-thyroid drug treatment for several months successfully relieved symptoms in one subject, whereas the remaining patients required total thyroidectomy to control their disease. This is the first Jordanian family with familial non-autoimmune hyperthyroidism, with mutations affecting the TSHR gene.

Follicular Variant of Papillary Thyroid Carcinoma Presenting as Toxic Nodule in an Adolescent: Coexistent Polymorphism of the TSHR and Gsα Genes

“…The same SNPs were identified in two family members: the father was heterozygous for the TSHR polymorphism but wild type for Gsa, while the mother was heterozygous for the Gsa polymorphism and wild type for the TSHR variant. Of interest, the TSHR SNP was found to be associated with familial nonautoimmune hyperthyroidism, as well as with AFTNs (32,33). To the best of our knowledge, no other data are available in the literature about the prevalence of each of the two SNPs in AFTNs as well as in the general population.…”

Characteristics of Thyrotoxicosis Among Thyroid Patients and their Quality of life in a Teaching Hospital in Jordan: A Crosssectional Study

“… 18 , 19 In Jordan, a study conducted in 2009 by Ismail et al reported on the detection of combined genomic variants in families with hyperthyroidism. 20 …”