Sorting Variants of Unknown Significance Identified by Whole Exome Sequencing: Genetic and Laboratory Investigations of Two Novel MCT8 Variants

Jiao Fu, Manassawee Korwutthikulrangsri, Leigh Ramos-Platt, Tyler M. Pierson, Xiao Hui Liao, Samuel Refetoff, Roy E. Weiss, Alexandra M. Dumitrescu

Research output: Contribution to journalArticle

Abstract

Mutations in the cell membrane thyroid hormone (TH) transporter monocarboxylate transporter (MCT) 8 produce severe neuropsychomotor defects and characteristic thyroid function test (TFT) abnormalities. Two children with mild neurological phenotypes and normal TFTs were found to harbor MCT8 gene variants of unknown significance (VUS), MCT8-R388Q that occurred de novo, and MCT8-Q212E. Normal TH transport and action in fibroblasts of MCT8-R388Q was demonstrated in a novel nonradioactive functional assay measuring the intracellular TH availability after L-T3 treatment. No genotype-phenotype correlation was found in additional family members carrying MCT8-Q212E. For the field of MCT8 deficiency, it is important to assess the significance of MCT8 gene VUS.

Original languageEnglish (US)
Pages (from-to)463-465
Number of pages3
JournalThyroid
Volume30
Issue number3
DOIs
StatePublished - Mar 2020

Keywords

  • Allan-Herndon-Dudley syndrome
  • MCT8
  • thyroid hormone transporter
  • variants of unknown significance
  • whole exome sequencing

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Sorting Variants of Unknown Significance Identified by Whole Exome Sequencing: Genetic and Laboratory Investigations of Two Novel MCT8 Variants'. Together they form a unique fingerprint.

  • Cite this

    Fu, J., Korwutthikulrangsri, M., Ramos-Platt, L., Pierson, T. M., Liao, X. H., Refetoff, S., Weiss, R. E., & Dumitrescu, A. M. (2020). Sorting Variants of Unknown Significance Identified by Whole Exome Sequencing: Genetic and Laboratory Investigations of Two Novel MCT8 Variants. Thyroid, 30(3), 463-465. https://doi.org/10.1089/thy.2018.0703