Mutations in TBL1X Are Associated With Central Hypothyroidism.
Isolated congenital central hypothyroidism (CeH) can result from mutations in TRHR, TSHB, and IGSF1, but its etiology often remains unexplained. We identified a missense mutation in the transducin β-like protein 1, X-linked (TBL1X) gene in three relatives diagnosed with isolated CeH. TBL1X is part of the thyroid hormone receptor-corepressor complex.



The objectives of the study were the identification of TBL1X mutations in patients with unexplained isolated CeH, Sanger sequencing of relatives of affected individuals, and clinical and biochemical characterization; in vitro investigation of functional consequences of mutations; and mRNA expression in, and immunostaining of, human hypothalami and pituitary glands.



This was an observational study.



The study was conducted at university medical centers.



Nineteen individuals with and seven without a mutation participated in the study.



Outcome measures included sequencing results, clinical and biochemical characteristics of mutation carriers, and results of in vitro functional and expression studies.



Sanger sequencing yielded five additional mutations. All patients (n = 8; six males) were previously diagnosed with CeH (free T4[FT4] concentration below the reference interval, normal thyrotropin). Eleven relatives (two males) also carried mutations. One female had CeH, whereas 10 others had low-normal FT4 concentrations. As a group, adult mutation carriers had 20%-25% lower FT4 concentrations than controls. Twelve of 19 evaluated carriers had hearing loss. Mutations are located in the highly conserved WD40-repeat domain of the protein, influencing its expression and thermal stability. TBL1X mRNA and protein are expressed in the human hypothalamus and pituitary.



TBL1X mutations are associated with CeH and hearing loss. FT4 concentrations in mutation carriers vary from low-normal to values compatible with CeH.
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Charlotte A
CA
Heinen
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Monique
M
Losekoot
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Yu
Y
Sun
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Peter J
PJ
Watson
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Louise
L
Fairall
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Sjoerd D
SD
Joustra
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Nitash
N
Zwaveling-Soonawala
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Wilma
W
Oostdijk
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Erica L T
EL
van den Akker
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Mariëlle
M
Alders
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Gijs W E
GW
Santen
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Rick R
RR
van Rijn
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Wouter A
WA
Dreschler
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Olga V
OV
Surovtseva
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Nienke R
NR
Biermasz
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Raoul C
RC
Hennekam
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Jan M
JM
Wit
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
John W R
JW
Schwabe
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Anita
A
Boelen
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
Eric
E
Fliers
Department of Endocrinology and Metabolism (C.A.H., O.V.S., A.B., E.F.), Clinical Genetics (M.A.), and Clinical and Experimental Audiology (W.A.D.), Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Paediatric Endocrinology (C.A.H., N.Z.-S., A.S.P.v.T.), Radiology (R.R.v.R.), and Paediatrics (R.C.H.), Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Departments of Clinical Genetics (M.L., Y.S., G.W.E.S.), Paediatrics (S.D.J., W.O., J.M.W.), and Endocrinology and Metabolism (S.D.J., N.R.B.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Henry Wellcome Laboratories of Structural Biology (P.J.W., L.F., J.W.R.S.), Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, United Kingdom; and Department of Paediatric Endocrinology (E.L.T.v.d.A.), Erasmus Medical Centre, 3000 CB Rotterdam, The Netherlands.
A S Paul
AS
van Trotsenburg
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D034381:Hearing Loss / Q000209:etiology / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000235:genetics*; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010902:Pituitary Gland / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013974:Thyroxine / Q000097:blood*; D015293:Transducin / Q000235:genetics*; D055815:Young Adult
D012333:RNA, Messenger; C119542:TBL1X protein, human; D015293:Transducin; D013974:Thyroxine