A family with hypothyroidism caused by fatty acid synthase and apolipoprotein B receptor mutations

Sun,Jianhua; Sun,Lizhi; Chen,Weijie; Yin,Xiao; Lu,Yong; Jiang,Qiang

doi:10.3892/mmr.2018.9499

A family with hypothyroidism caused by fatty acid synthase and apolipoprotein B receptor mutations

Authors:
- Jianhua Sun
- Lizhi Sun
- Weijie Chen
- Xiao Yin
- Yong Lu
- Qiang Jiang
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Affiliations: Department of Oncology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China, Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China
Published online on: September 20, 2018 https://doi.org/10.3892/mmr.2018.9499
Pages: 4904-4912
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Hypothyroidism is a disease with a genetic component. The present study aimed to identify the potential causative gene mutation in a family with hypothyroidism and to investigate its potential pathology. DNA was extracted from the affected individual and his parents, maternal aunt and maternal grandmother. Whole exome sequencing was used to examine their exomes. The potential causative genes that may have an autosomal dominant mode of inheritance were selected after variant calling and filtering. Bioinformatics analysis was utilized to predict the deleteriousness of the identified variants, and multiple sequence alignment and conserved protein domain analyses were performed using online software. Finally, Sanger sequencing was used to validate the identified variants. In the present study, a total of 50 variants were screened based on the autosomal dominant mode of inheritance. Two variants, the fatty acid synthase (FASN) and apolipoprotein B receptor (APOBR) genes, were further analyzed, as they were highly associated with hypothyroidism. Genotyping results revealed that two mutations, c.G7192T (p.A2398S) in the FASN gene and c.C1883G (p.T628R) in the APOBR gene, were fully co‑segregated with established hypothyroidism phenotypes in the family. These mutations were located in the conserved α/β‑hydrolase fold and Na+/Ca2+ exchanger superfamily domain of FASN and APOBR, respectively. In conclusion, the present study demonstrated that the FASN c.G7192T and APOBR c.C1883G mutations may be the potential causative variants in this Chinese hypothyroidism pedigree.

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