TY - JOUR
T1 - Sorting Variants of Unknown Significance Identified by Whole Exome Sequencing
T2 - Genetic and Laboratory Investigations of Two Novel MCT8 Variants
AU - Fu, Jiao
AU - Korwutthikulrangsri, Manassawee
AU - Ramos-Platt, Leigh
AU - Pierson, Tyler M.
AU - Liao, Xiao Hui
AU - Refetoff, Samuel
AU - Weiss, Roy E.
AU - Dumitrescu, Alexandra M.
N1 - Funding Information:
funds for Thyroid Research to R.E.W. and an Award from China Scholarship Council to J.F.
Funding Information:
This study was supported, in part, by grants DK110322 to A.M.D. and DK15070 to S.R., from the National Institutes of Health, The Seymour J. Abrams and Rabbi Morris Esformes funds for Thyroid Research to R.E.W. and an Award from China Scholarship Council to J.F.
Funding Information:
This study was supported, in part, by grants DK110322 to A.M.D. and DK15070 to S.R., from the National Institutes of Health, The Seymour J. Abrams and Rabbi Morris Esformes
Publisher Copyright:
© Copyright 2020, Mary Ann Liebert, Inc., publishers.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Allan-Herndon-Dudley syndrome
KW - MCT8
KW - thyroid hormone transporter
KW - variants of unknown significance
KW - whole exome sequencing
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U2 - 10.1089/thy.2018.0703
DO - 10.1089/thy.2018.0703
M3 - Article
C2 - 31856685
AN - SCOPUS:85081944935
VL - 30
SP - 463
EP - 465
JO - Thyroid
JF - Thyroid
SN - 1050-7256
IS - 3
ER -