Association of an X-chromosome dodecamer insertional variant allele with mental retardation
Mental retardation is a prominent feature of many neurodevelopmental syndromes. In an attempt to identify genetic components of these illnesses, we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these cosmids, Cos-4, maps to the X...
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| Veröffentlicht in: | Molecular psychiatry 1998-07, Vol.3 (4), p.303-309 |
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| creator | Philibert, R A King, B H Winfield, S Cook, E H Lee, Y-H Stubblefield, B Damschroder-Williams, P Dea, C Palotie, A Tengstrom, C Martin, B M Ginns, E I |
| description | Mental retardation is a prominent feature of many neurodevelopmental syndromes. In an attempt to identify genetic components of these illnesses, we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these cosmids, Cos-4, maps to the X-chromosome and contains the sequence of a 7.3-kb mRNA. Initial polymorphism analysis across a region of repetitive DNA in this gene revealed a rare 12-bp exonic variation (1% in non-ill males) having an increased prevalence in non-Fragile X males with mental retardation (4%,
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| doi_str_mv | 10.1038/sj.mp.4000442 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73836170</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2645751125</sourcerecordid><originalsourceid>FETCH-LOGICAL-c454t-18696b23f18e736bba27960d27a9bca82c684983c29a3aa2252045450e7f717b3</originalsourceid><addsrcrecordid>eNqFkU1rFTEUhoMota0uXQoBxd1c853MshS1QqEbC4KLcCaTsXOZTK45cxX_vbm9gwURukrgefLmHF5CXnG24Uy697jdpN1GMcaUEk_IKVfWNFpb97TepW4bxZ16Ts4Qt4wdoD4hJ61lwkp3Sr5dIOYwwjLmmeaBwky_NuGu5JQxp0j73McAKRY6zhjLQYOJ_oQywrxQmKY4RfprXO5oivNSUYkLlP4-7wV5NsCE8eV6npPbjx--XF411zefPl9eXDdBabU03JnWdEIO3EUrTdeBsK1hvbDQdgGcCMap1skgWpAAQmjB6kPNoh0st508J--OubuSf-wjLj6NGOI0wRzzHn1dVBpu2aMit4Jzw2wV3_wjbvO-1M3RC6O01ZwLXa3maIWSEUsc_K6MCcpvz5k_dONx69POr91U__Wauu9S7P_aaxmVv105YIBpKDCHER9CndTK8aptjhpWMn-P5WG4___7B-bppaw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2645751125</pqid></control><display><type>article</type><title>Association of an X-chromosome dodecamer insertional variant allele with mental retardation</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Philibert, R A ; King, B H ; Winfield, S ; Cook, E H ; Lee, Y-H ; Stubblefield, B ; Damschroder-Williams, P ; Dea, C ; Palotie, A ; Tengstrom, C ; Martin, B M ; Ginns, E I</creator><creatorcontrib>Philibert, R A ; King, B H ; Winfield, S ; Cook, E H ; Lee, Y-H ; Stubblefield, B ; Damschroder-Williams, P ; Dea, C ; Palotie, A ; Tengstrom, C ; Martin, B M ; Ginns, E I</creatorcontrib><description>Mental retardation is a prominent feature of many neurodevelopmental syndromes. In an attempt to identify genetic components of these illnesses, we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these cosmids, Cos-4, maps to the X-chromosome and contains the sequence of a 7.3-kb mRNA. Initial polymorphism analysis across a region of repetitive DNA in this gene revealed a rare 12-bp exonic variation (1% in non-ill males) having an increased prevalence in non-Fragile X males with mental retardation (4%,
P
<0.04,
n
= 81). This variant was not present in the highly conserved mouse homologue that has 100% amino acid identity to the human sequence near the polymorphism. Subsequent screening of two additional independent cohorts of non-Fragile X mentally retarded patients and ethnically matched controls demonstrated an even higher prevalence of the 12-bp variant in males with mental retardation (8%,
P
<0.0003,
n
= 125, and 14%,
P
<0.10,
n
= 36)
vs
the controls. Multivariate analysis was conducted in an effort to identify other phenotypic components in affected individuals, and the findings suggested an increased incidence of histories of hypothyroidism (
P
<0.001) and treatment with antidepressants (
P
<0.001). we conclude that the presence of this 12-bp variant confers significant susceptibility for mental retardation.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/sj.mp.4000442</identifier><identifier>PMID: 9702738</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adult and adolescent clinical studies ; Alleles ; Amino Acid Sequence ; Animals ; Antidepressants ; Base Sequence ; Behavioral Sciences ; Biological and medical sciences ; Biological Psychology ; California - epidemiology ; Chromosome Mapping ; Conserved Sequence ; Cosmids ; DNA Transposable Elements ; Europe - epidemiology ; Exons ; Female ; Finland - epidemiology ; Fragile X syndrome ; Fragile X Syndrome - genetics ; Gene Library ; Gene mapping ; Gene polymorphism ; Genetic Variation ; Humans ; Hypothyroidism ; Hypothyroidism - epidemiology ; Hypothyroidism - genetics ; immediate-communication ; In Situ Hybridization, Fluorescence ; Intellectual deficiency ; Intellectual disabilities ; Intellectual Disability - genetics ; Male ; Males ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Molecular Sequence Data ; mRNA ; Multivariate analysis ; Neurosciences ; Pharmacotherapy ; Polymorphism ; Polymorphism, Genetic ; Prevalence ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Sequence Alignment ; Sequence Homology, Amino Acid ; Trinucleotide Repeats ; X Chromosome ; X chromosomes</subject><ispartof>Molecular psychiatry, 1998-07, Vol.3 (4), p.303-309</ispartof><rights>Macmillan Publishers Limited 1998</rights><rights>1999 INIST-CNRS</rights><rights>Macmillan Publishers Limited 1998.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-18696b23f18e736bba27960d27a9bca82c684983c29a3aa2252045450e7f717b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.mp.4000442$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.mp.4000442$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1835481$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9702738$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Philibert, R A</creatorcontrib><creatorcontrib>King, B H</creatorcontrib><creatorcontrib>Winfield, S</creatorcontrib><creatorcontrib>Cook, E H</creatorcontrib><creatorcontrib>Lee, Y-H</creatorcontrib><creatorcontrib>Stubblefield, B</creatorcontrib><creatorcontrib>Damschroder-Williams, P</creatorcontrib><creatorcontrib>Dea, C</creatorcontrib><creatorcontrib>Palotie, A</creatorcontrib><creatorcontrib>Tengstrom, C</creatorcontrib><creatorcontrib>Martin, B M</creatorcontrib><creatorcontrib>Ginns, E I</creatorcontrib><title>Association of an X-chromosome dodecamer insertional variant allele with mental retardation</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Mental retardation is a prominent feature of many neurodevelopmental syndromes. In an attempt to identify genetic components of these illnesses, we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these cosmids, Cos-4, maps to the X-chromosome and contains the sequence of a 7.3-kb mRNA. Initial polymorphism analysis across a region of repetitive DNA in this gene revealed a rare 12-bp exonic variation (1% in non-ill males) having an increased prevalence in non-Fragile X males with mental retardation (4%,
P
<0.04,
n
= 81). This variant was not present in the highly conserved mouse homologue that has 100% amino acid identity to the human sequence near the polymorphism. Subsequent screening of two additional independent cohorts of non-Fragile X mentally retarded patients and ethnically matched controls demonstrated an even higher prevalence of the 12-bp variant in males with mental retardation (8%,
P
<0.0003,
n
= 125, and 14%,
P
<0.10,
n
= 36)
vs
the controls. Multivariate analysis was conducted in an effort to identify other phenotypic components in affected individuals, and the findings suggested an increased incidence of histories of hypothyroidism (
P
<0.001) and treatment with antidepressants (
P
<0.001). we conclude that the presence of this 12-bp variant confers significant susceptibility for mental retardation.</description><subject>Adult and adolescent clinical studies</subject><subject>Alleles</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antidepressants</subject><subject>Base Sequence</subject><subject>Behavioral Sciences</subject><subject>Biological and medical sciences</subject><subject>Biological Psychology</subject><subject>California - epidemiology</subject><subject>Chromosome Mapping</subject><subject>Conserved Sequence</subject><subject>Cosmids</subject><subject>DNA Transposable Elements</subject><subject>Europe - epidemiology</subject><subject>Exons</subject><subject>Female</subject><subject>Finland - epidemiology</subject><subject>Fragile X syndrome</subject><subject>Fragile X Syndrome - genetics</subject><subject>Gene Library</subject><subject>Gene mapping</subject><subject>Gene polymorphism</subject><subject>Genetic Variation</subject><subject>Humans</subject><subject>Hypothyroidism</subject><subject>Hypothyroidism - epidemiology</subject><subject>Hypothyroidism - genetics</subject><subject>immediate-communication</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Intellectual deficiency</subject><subject>Intellectual disabilities</subject><subject>Intellectual Disability - genetics</subject><subject>Male</subject><subject>Males</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>mRNA</subject><subject>Multivariate analysis</subject><subject>Neurosciences</subject><subject>Pharmacotherapy</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Prevalence</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Sequence Alignment</subject><subject>Sequence Homology, Amino Acid</subject><subject>Trinucleotide Repeats</subject><subject>X Chromosome</subject><subject>X chromosomes</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rFTEUhoMota0uXQoBxd1c853MshS1QqEbC4KLcCaTsXOZTK45cxX_vbm9gwURukrgefLmHF5CXnG24Uy697jdpN1GMcaUEk_IKVfWNFpb97TepW4bxZ16Ts4Qt4wdoD4hJ61lwkp3Sr5dIOYwwjLmmeaBwky_NuGu5JQxp0j73McAKRY6zhjLQYOJ_oQywrxQmKY4RfprXO5oivNSUYkLlP4-7wV5NsCE8eV6npPbjx--XF411zefPl9eXDdBabU03JnWdEIO3EUrTdeBsK1hvbDQdgGcCMap1skgWpAAQmjB6kPNoh0st508J--OubuSf-wjLj6NGOI0wRzzHn1dVBpu2aMit4Jzw2wV3_wjbvO-1M3RC6O01ZwLXa3maIWSEUsc_K6MCcpvz5k_dONx69POr91U__Wauu9S7P_aaxmVv105YIBpKDCHER9CndTK8aptjhpWMn-P5WG4___7B-bppaw</recordid><startdate>19980701</startdate><enddate>19980701</enddate><creator>Philibert, R A</creator><creator>King, B H</creator><creator>Winfield, S</creator><creator>Cook, E H</creator><creator>Lee, Y-H</creator><creator>Stubblefield, B</creator><creator>Damschroder-Williams, P</creator><creator>Dea, C</creator><creator>Palotie, A</creator><creator>Tengstrom, C</creator><creator>Martin, B M</creator><creator>Ginns, E I</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>7TK</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>19980701</creationdate><title>Association of an X-chromosome dodecamer insertional variant allele with mental retardation</title><author>Philibert, R A ; King, B H ; Winfield, S ; Cook, E H ; Lee, Y-H ; Stubblefield, B ; Damschroder-Williams, P ; Dea, C ; Palotie, A ; Tengstrom, C ; Martin, B M ; Ginns, E I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-18696b23f18e736bba27960d27a9bca82c684983c29a3aa2252045450e7f717b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Alleles</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antidepressants</topic><topic>Base Sequence</topic><topic>Behavioral Sciences</topic><topic>Biological and medical sciences</topic><topic>Biological Psychology</topic><topic>California - epidemiology</topic><topic>Chromosome Mapping</topic><topic>Conserved Sequence</topic><topic>Cosmids</topic><topic>DNA Transposable Elements</topic><topic>Europe - epidemiology</topic><topic>Exons</topic><topic>Female</topic><topic>Finland - epidemiology</topic><topic>Fragile X syndrome</topic><topic>Fragile X Syndrome - genetics</topic><topic>Gene Library</topic><topic>Gene mapping</topic><topic>Gene polymorphism</topic><topic>Genetic Variation</topic><topic>Humans</topic><topic>Hypothyroidism</topic><topic>Hypothyroidism - epidemiology</topic><topic>Hypothyroidism - genetics</topic><topic>immediate-communication</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Intellectual deficiency</topic><topic>Intellectual disabilities</topic><topic>Intellectual Disability - genetics</topic><topic>Male</topic><topic>Males</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>mRNA</topic><topic>Multivariate analysis</topic><topic>Neurosciences</topic><topic>Pharmacotherapy</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Prevalence</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Sequence Alignment</topic><topic>Sequence Homology, Amino Acid</topic><topic>Trinucleotide Repeats</topic><topic>X Chromosome</topic><topic>X chromosomes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Philibert, R A</creatorcontrib><creatorcontrib>King, B H</creatorcontrib><creatorcontrib>Winfield, S</creatorcontrib><creatorcontrib>Cook, E H</creatorcontrib><creatorcontrib>Lee, Y-H</creatorcontrib><creatorcontrib>Stubblefield, B</creatorcontrib><creatorcontrib>Damschroder-Williams, P</creatorcontrib><creatorcontrib>Dea, C</creatorcontrib><creatorcontrib>Palotie, A</creatorcontrib><creatorcontrib>Tengstrom, C</creatorcontrib><creatorcontrib>Martin, B M</creatorcontrib><creatorcontrib>Ginns, E I</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Philibert, R A</au><au>King, B H</au><au>Winfield, S</au><au>Cook, E H</au><au>Lee, Y-H</au><au>Stubblefield, B</au><au>Damschroder-Williams, P</au><au>Dea, C</au><au>Palotie, A</au><au>Tengstrom, C</au><au>Martin, B M</au><au>Ginns, E I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of an X-chromosome dodecamer insertional variant allele with mental retardation</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>1998-07-01</date><risdate>1998</risdate><volume>3</volume><issue>4</issue><spage>303</spage><epage>309</epage><pages>303-309</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>Mental retardation is a prominent feature of many neurodevelopmental syndromes. In an attempt to identify genetic components of these illnesses, we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these cosmids, Cos-4, maps to the X-chromosome and contains the sequence of a 7.3-kb mRNA. Initial polymorphism analysis across a region of repetitive DNA in this gene revealed a rare 12-bp exonic variation (1% in non-ill males) having an increased prevalence in non-Fragile X males with mental retardation (4%,
P
<0.04,
n
= 81). This variant was not present in the highly conserved mouse homologue that has 100% amino acid identity to the human sequence near the polymorphism. Subsequent screening of two additional independent cohorts of non-Fragile X mentally retarded patients and ethnically matched controls demonstrated an even higher prevalence of the 12-bp variant in males with mental retardation (8%,
P
<0.0003,
n
= 125, and 14%,
P
<0.10,
n
= 36)
vs
the controls. Multivariate analysis was conducted in an effort to identify other phenotypic components in affected individuals, and the findings suggested an increased incidence of histories of hypothyroidism (
P
<0.001) and treatment with antidepressants (
P
<0.001). we conclude that the presence of this 12-bp variant confers significant susceptibility for mental retardation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>9702738</pmid><doi>10.1038/sj.mp.4000442</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1359-4184 |
| ispartof | Molecular psychiatry, 1998-07, Vol.3 (4), p.303-309 |
| issn | 1359-4184 1476-5578 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73836170 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adult and adolescent clinical studies Alleles Amino Acid Sequence Animals Antidepressants Base Sequence Behavioral Sciences Biological and medical sciences Biological Psychology California - epidemiology Chromosome Mapping Conserved Sequence Cosmids DNA Transposable Elements Europe - epidemiology Exons Female Finland - epidemiology Fragile X syndrome Fragile X Syndrome - genetics Gene Library Gene mapping Gene polymorphism Genetic Variation Humans Hypothyroidism Hypothyroidism - epidemiology Hypothyroidism - genetics immediate-communication In Situ Hybridization, Fluorescence Intellectual deficiency Intellectual disabilities Intellectual Disability - genetics Male Males Medical sciences Medicine Medicine & Public Health Mice Molecular Sequence Data mRNA Multivariate analysis Neurosciences Pharmacotherapy Polymorphism Polymorphism, Genetic Prevalence Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Sequence Alignment Sequence Homology, Amino Acid Trinucleotide Repeats X Chromosome X chromosomes |
| title | Association of an X-chromosome dodecamer insertional variant allele with mental retardation |
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