Psychomotor Retardation Caused by a Defective Thyroid Hormone Transporter: Report of Two Families with Different MCT8 Mutations
Background/Aims: Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two...
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| Veröffentlicht in: | Hormone research in paediatrics 2014-01, Vol.82 (4), p.261-271 |
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| creator | Anık, Ahmet Kersseboom, Simone Demir, Korcan Çatlı, Gönül Yiş, Uluç Böber, Ece van Mullem, Alies van Herebeek, Ramona E.A. Hız, Semra Abacı, Ayhan Visser, Theo J. |
| description | Background/Aims: Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings. Case Report and Results: We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context. Conclusion: Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS. |
| doi_str_mv | 10.1159/000365191 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_25247785</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1610762796</sourcerecordid><originalsourceid>FETCH-LOGICAL-c362t-8c78d6028f61e754d619037aafda75dfb4af462213e28b3937fc94e0b65982bd3</originalsourceid><addsrcrecordid>eNpt0UFv0zAUB3ALMbFp7MAdIUu7sEOZn53YDjfUMYq0iWkq58iJn6lHE3e2w9TTvjopHTlMO_lZ_r33LP0JeQfsE0BZnTPGhCyhglfkCKQUM665fD3VoA_JSUp3bOe0qkC9IYe85IVSujwijzdp265CF3KI9BazidZkH3o6N0NCS5stNfQCHbbZ_0G6XG1j8JYuQuxCP96j6dMmxIzx89i-q2hwdPkQ6KXp_Npjog8-r-iFdw4j9plez5eaXg_535r0lhw4s0548nQek5-XX5fzxezqx7fv8y9Xs1ZInme6VdpKxrWTgKosrISKCWWMs0aV1jWFcYXkHARy3YhKKNdWBbJGlpXmjRXH5ON-7iaG-wFTrjufWlyvTY9hSDVIYEpyVcmRnj6jd2GI_fi7UXEFIAoJozrbqzaGlCK6ehN9Z-K2BlbvgqmnYEb74Wni0HRoJ_k_hhG834PfJv7COIGp__TF58XtzV7UG-vEXwUJnJc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1627113461</pqid></control><display><type>article</type><title>Psychomotor Retardation Caused by a Defective Thyroid Hormone Transporter: Report of Two Families with Different MCT8 Mutations</title><source>MEDLINE</source><source>Karger Journals</source><source>Alma/SFX Local Collection</source><creator>Anık, Ahmet ; Kersseboom, Simone ; Demir, Korcan ; Çatlı, Gönül ; Yiş, Uluç ; Böber, Ece ; van Mullem, Alies ; van Herebeek, Ramona E.A. ; Hız, Semra ; Abacı, Ayhan ; Visser, Theo J.</creator><creatorcontrib>Anık, Ahmet ; Kersseboom, Simone ; Demir, Korcan ; Çatlı, Gönül ; Yiş, Uluç ; Böber, Ece ; van Mullem, Alies ; van Herebeek, Ramona E.A. ; Hız, Semra ; Abacı, Ayhan ; Visser, Theo J.</creatorcontrib><description>Background/Aims: Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings. Case Report and Results: We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context. Conclusion: Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.</description><identifier>ISSN: 1663-2818</identifier><identifier>EISSN: 1663-2826</identifier><identifier>DOI: 10.1159/000365191</identifier><identifier>PMID: 25247785</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Child ; Child, Preschool ; DNA Mutational Analysis ; Gene Deletion ; Humans ; Infant ; Intellectual Disability - etiology ; Intellectual Disability - genetics ; Male ; Mental Retardation, X-Linked - genetics ; Mental Retardation, X-Linked - metabolism ; Mental Retardation, X-Linked - psychology ; Monocarboxylic Acid Transporters - genetics ; Monocarboxylic Acid Transporters - metabolism ; Muscle Hypotonia - genetics ; Muscle Hypotonia - metabolism ; Muscle Hypotonia - psychology ; Muscular Atrophy - genetics ; Muscular Atrophy - metabolism ; Muscular Atrophy - psychology ; Mutation - genetics ; Mutation, Missense - genetics ; Original Paper ; Pedigree ; Thyroid Hormones - blood</subject><ispartof>Hormone research in paediatrics, 2014-01, Vol.82 (4), p.261-271</ispartof><rights>2014 S. Karger AG, Basel</rights><rights>2014 S. Karger AG, Basel.</rights><rights>Copyright (c) 2014 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-8c78d6028f61e754d619037aafda75dfb4af462213e28b3937fc94e0b65982bd3</citedby><cites>FETCH-LOGICAL-c362t-8c78d6028f61e754d619037aafda75dfb4af462213e28b3937fc94e0b65982bd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2422,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25247785$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anık, Ahmet</creatorcontrib><creatorcontrib>Kersseboom, Simone</creatorcontrib><creatorcontrib>Demir, Korcan</creatorcontrib><creatorcontrib>Çatlı, Gönül</creatorcontrib><creatorcontrib>Yiş, Uluç</creatorcontrib><creatorcontrib>Böber, Ece</creatorcontrib><creatorcontrib>van Mullem, Alies</creatorcontrib><creatorcontrib>van Herebeek, Ramona E.A.</creatorcontrib><creatorcontrib>Hız, Semra</creatorcontrib><creatorcontrib>Abacı, Ayhan</creatorcontrib><creatorcontrib>Visser, Theo J.</creatorcontrib><title>Psychomotor Retardation Caused by a Defective Thyroid Hormone Transporter: Report of Two Families with Different MCT8 Mutations</title><title>Hormone research in paediatrics</title><addtitle>Horm Res Paediatr</addtitle><description>Background/Aims: Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings. Case Report and Results: We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context. Conclusion: Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.</description><subject>Child</subject><subject>Child, Preschool</subject><subject>DNA Mutational Analysis</subject><subject>Gene Deletion</subject><subject>Humans</subject><subject>Infant</subject><subject>Intellectual Disability - etiology</subject><subject>Intellectual Disability - genetics</subject><subject>Male</subject><subject>Mental Retardation, X-Linked - genetics</subject><subject>Mental Retardation, X-Linked - metabolism</subject><subject>Mental Retardation, X-Linked - psychology</subject><subject>Monocarboxylic Acid Transporters - genetics</subject><subject>Monocarboxylic Acid Transporters - metabolism</subject><subject>Muscle Hypotonia - genetics</subject><subject>Muscle Hypotonia - metabolism</subject><subject>Muscle Hypotonia - psychology</subject><subject>Muscular Atrophy - genetics</subject><subject>Muscular Atrophy - metabolism</subject><subject>Muscular Atrophy - psychology</subject><subject>Mutation - genetics</subject><subject>Mutation, Missense - genetics</subject><subject>Original Paper</subject><subject>Pedigree</subject><subject>Thyroid Hormones - blood</subject><issn>1663-2818</issn><issn>1663-2826</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpt0UFv0zAUB3ALMbFp7MAdIUu7sEOZn53YDjfUMYq0iWkq58iJn6lHE3e2w9TTvjopHTlMO_lZ_r33LP0JeQfsE0BZnTPGhCyhglfkCKQUM665fD3VoA_JSUp3bOe0qkC9IYe85IVSujwijzdp265CF3KI9BazidZkH3o6N0NCS5stNfQCHbbZ_0G6XG1j8JYuQuxCP96j6dMmxIzx89i-q2hwdPkQ6KXp_Npjog8-r-iFdw4j9plez5eaXg_535r0lhw4s0548nQek5-XX5fzxezqx7fv8y9Xs1ZInme6VdpKxrWTgKosrISKCWWMs0aV1jWFcYXkHARy3YhKKNdWBbJGlpXmjRXH5ON-7iaG-wFTrjufWlyvTY9hSDVIYEpyVcmRnj6jd2GI_fi7UXEFIAoJozrbqzaGlCK6ehN9Z-K2BlbvgqmnYEb74Wni0HRoJ_k_hhG834PfJv7COIGp__TF58XtzV7UG-vEXwUJnJc</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Anık, Ahmet</creator><creator>Kersseboom, Simone</creator><creator>Demir, Korcan</creator><creator>Çatlı, Gönül</creator><creator>Yiş, Uluç</creator><creator>Böber, Ece</creator><creator>van Mullem, Alies</creator><creator>van Herebeek, Ramona E.A.</creator><creator>Hız, Semra</creator><creator>Abacı, Ayhan</creator><creator>Visser, Theo J.</creator><general>S. Karger AG</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20140101</creationdate><title>Psychomotor Retardation Caused by a Defective Thyroid Hormone Transporter: Report of Two Families with Different MCT8 Mutations</title><author>Anık, Ahmet ; Kersseboom, Simone ; Demir, Korcan ; Çatlı, Gönül ; Yiş, Uluç ; Böber, Ece ; van Mullem, Alies ; van Herebeek, Ramona E.A. ; Hız, Semra ; Abacı, Ayhan ; Visser, Theo J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-8c78d6028f61e754d619037aafda75dfb4af462213e28b3937fc94e0b65982bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Child</topic><topic>Child, Preschool</topic><topic>DNA Mutational Analysis</topic><topic>Gene Deletion</topic><topic>Humans</topic><topic>Infant</topic><topic>Intellectual Disability - etiology</topic><topic>Intellectual Disability - genetics</topic><topic>Male</topic><topic>Mental Retardation, X-Linked - genetics</topic><topic>Mental Retardation, X-Linked - metabolism</topic><topic>Mental Retardation, X-Linked - psychology</topic><topic>Monocarboxylic Acid Transporters - genetics</topic><topic>Monocarboxylic Acid Transporters - metabolism</topic><topic>Muscle Hypotonia - genetics</topic><topic>Muscle Hypotonia - metabolism</topic><topic>Muscle Hypotonia - psychology</topic><topic>Muscular Atrophy - genetics</topic><topic>Muscular Atrophy - metabolism</topic><topic>Muscular Atrophy - psychology</topic><topic>Mutation - genetics</topic><topic>Mutation, Missense - genetics</topic><topic>Original Paper</topic><topic>Pedigree</topic><topic>Thyroid Hormones - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anık, Ahmet</creatorcontrib><creatorcontrib>Kersseboom, Simone</creatorcontrib><creatorcontrib>Demir, Korcan</creatorcontrib><creatorcontrib>Çatlı, Gönül</creatorcontrib><creatorcontrib>Yiş, Uluç</creatorcontrib><creatorcontrib>Böber, Ece</creatorcontrib><creatorcontrib>van Mullem, Alies</creatorcontrib><creatorcontrib>van Herebeek, Ramona E.A.</creatorcontrib><creatorcontrib>Hız, Semra</creatorcontrib><creatorcontrib>Abacı, Ayhan</creatorcontrib><creatorcontrib>Visser, Theo J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Hormone research in paediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anık, Ahmet</au><au>Kersseboom, Simone</au><au>Demir, Korcan</au><au>Çatlı, Gönül</au><au>Yiş, Uluç</au><au>Böber, Ece</au><au>van Mullem, Alies</au><au>van Herebeek, Ramona E.A.</au><au>Hız, Semra</au><au>Abacı, Ayhan</au><au>Visser, Theo J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Psychomotor Retardation Caused by a Defective Thyroid Hormone Transporter: Report of Two Families with Different MCT8 Mutations</atitle><jtitle>Hormone research in paediatrics</jtitle><addtitle>Horm Res Paediatr</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>82</volume><issue>4</issue><spage>261</spage><epage>271</epage><pages>261-271</pages><issn>1663-2818</issn><eissn>1663-2826</eissn><abstract>Background/Aims: Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings. Case Report and Results: We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context. Conclusion: Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>25247785</pmid><doi>10.1159/000365191</doi><tpages>11</tpages></addata></record> |
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| subjects | Child Child, Preschool DNA Mutational Analysis Gene Deletion Humans Infant Intellectual Disability - etiology Intellectual Disability - genetics Male Mental Retardation, X-Linked - genetics Mental Retardation, X-Linked - metabolism Mental Retardation, X-Linked - psychology Monocarboxylic Acid Transporters - genetics Monocarboxylic Acid Transporters - metabolism Muscle Hypotonia - genetics Muscle Hypotonia - metabolism Muscle Hypotonia - psychology Muscular Atrophy - genetics Muscular Atrophy - metabolism Muscular Atrophy - psychology Mutation - genetics Mutation, Missense - genetics Original Paper Pedigree Thyroid Hormones - blood |
| title | Psychomotor Retardation Caused by a Defective Thyroid Hormone Transporter: Report of Two Families with Different MCT8 Mutations |
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