Childhood Hypophosphatasia Due to a de Novo Missense Mutation in the Tissue-Nonspecific Alkaline Phosphatase Gene
Hypophosphatasia is an inherited disorder due to mutations in the bone alkaline phosphatase (ALPL) gene. We report here a patient with childhood hypophosphatasia diagnosed at 1.4 yr because of pectus excavatum, large anterior fontanel, rachitic skeletal changes, and low serum alkaline phosphatase. S...
Gespeichert in:
| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2005-04, Vol.90 (4), p.2436-2439 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2439 |
|---|---|
| container_issue | 4 |
| container_start_page | 2436 |
| container_title | The journal of clinical endocrinology and metabolism |
| container_volume | 90 |
| creator | Taillandier, A. Sallinen, S.-L. Brun-Heath, I. De Mazancourt, P. Serre, J.-L. Mornet, E. |
| description | Hypophosphatasia is an inherited disorder due to mutations in the bone alkaline phosphatase (ALPL) gene. We report here a patient with childhood hypophosphatasia diagnosed at 1.4 yr because of pectus excavatum, large anterior fontanel, rachitic skeletal changes, and low serum alkaline phosphatase. Sequencing of the ALPL gene produced evidence of two distinct missense mutations, E174K (c.571G>A), of maternal origin, and a de novo mutation, M45I (c.186G>C). The study of various microsatellite polymorphisms ruled out false paternity and therefore confirmed that M45I occurred de novo in the paternal germline or in the early development of the patient. Site-directed mutagenesis showed that M45I results in the absence of in vitro alkaline phosphatase activity, suggesting that the mutation is a severe allele. In conclusion, childhood hypophosphatasia in this patient is the result of compound heterozygosity for the moderate mutation E174K and a novel severe de novo mutation M45I. |
| doi_str_mv | 10.1210/jc.2004-1456 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17351814</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17351814</sourcerecordid><originalsourceid>FETCH-LOGICAL-c428t-df6dfa6fefb56189a419f1549511638908d21eadef1413eae73b47db4580ab793</originalsourceid><addsrcrecordid>eNpt0L9v1DAYxnELgehR2JiRF5hI8ZvY-TFWB7RIbWEoEpvl2K8VHzk79Zsg9b8npzvRhcmDP3pe6cvYWxAXUIL4tLMXpRCyAKnqZ2wDnVRFA13znG2EKKHomvLXGXtFtBMCpFTVS3YGqm4ARLlhD9shjG5IyfHrxylNQ6JpMLOhYPjnBfmcuOEO-V36k_htIMJIyG-X2cwhRR4inwfk9-vHgsVdijShDT5Yfjn-NmOIyH_8m0R-hRFfsxfejIRvTu85-_n1y_32urj5fvVte3lTWFm2c-F87bypPfpe1dB2RkLnQclOAdRV24nWlYDGoQcJFRpsql42rpeqFaZvuuqcfTjuTjk9LEiz3geyOI4mYlpIQ1MpaEGu8OMR2pyIMno95bA3-VGD0IfEemf1IbE-JF75u9Pu0u_RPeFT0xW8PwFD1ow-m2gDPbm6bpsKDkPV0WF0yea11ZSRSO_SkuNa5v_n_wKkuZXK</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17351814</pqid></control><display><type>article</type><title>Childhood Hypophosphatasia Due to a de Novo Missense Mutation in the Tissue-Nonspecific Alkaline Phosphatase Gene</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Taillandier, A. ; Sallinen, S.-L. ; Brun-Heath, I. ; De Mazancourt, P. ; Serre, J.-L. ; Mornet, E.</creator><creatorcontrib>Taillandier, A. ; Sallinen, S.-L. ; Brun-Heath, I. ; De Mazancourt, P. ; Serre, J.-L. ; Mornet, E.</creatorcontrib><description>Hypophosphatasia is an inherited disorder due to mutations in the bone alkaline phosphatase (ALPL) gene. We report here a patient with childhood hypophosphatasia diagnosed at 1.4 yr because of pectus excavatum, large anterior fontanel, rachitic skeletal changes, and low serum alkaline phosphatase. Sequencing of the ALPL gene produced evidence of two distinct missense mutations, E174K (c.571G>A), of maternal origin, and a de novo mutation, M45I (c.186G>C). The study of various microsatellite polymorphisms ruled out false paternity and therefore confirmed that M45I occurred de novo in the paternal germline or in the early development of the patient. Site-directed mutagenesis showed that M45I results in the absence of in vitro alkaline phosphatase activity, suggesting that the mutation is a severe allele. In conclusion, childhood hypophosphatasia in this patient is the result of compound heterozygosity for the moderate mutation E174K and a novel severe de novo mutation M45I.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2004-1456</identifier><identifier>PMID: 15671102</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adolescent ; Alkaline Phosphatase - genetics ; Biological and medical sciences ; Endocrinopathies ; Fundamental and applied biological sciences. Psychology ; Humans ; Hypophosphatasia - genetics ; Male ; Medical sciences ; Mutation, Missense ; Vertebrates: endocrinology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2005-04, Vol.90 (4), p.2436-2439</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-df6dfa6fefb56189a419f1549511638908d21eadef1413eae73b47db4580ab793</citedby><cites>FETCH-LOGICAL-c428t-df6dfa6fefb56189a419f1549511638908d21eadef1413eae73b47db4580ab793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16687316$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15671102$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taillandier, A.</creatorcontrib><creatorcontrib>Sallinen, S.-L.</creatorcontrib><creatorcontrib>Brun-Heath, I.</creatorcontrib><creatorcontrib>De Mazancourt, P.</creatorcontrib><creatorcontrib>Serre, J.-L.</creatorcontrib><creatorcontrib>Mornet, E.</creatorcontrib><title>Childhood Hypophosphatasia Due to a de Novo Missense Mutation in the Tissue-Nonspecific Alkaline Phosphatase Gene</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Hypophosphatasia is an inherited disorder due to mutations in the bone alkaline phosphatase (ALPL) gene. We report here a patient with childhood hypophosphatasia diagnosed at 1.4 yr because of pectus excavatum, large anterior fontanel, rachitic skeletal changes, and low serum alkaline phosphatase. Sequencing of the ALPL gene produced evidence of two distinct missense mutations, E174K (c.571G>A), of maternal origin, and a de novo mutation, M45I (c.186G>C). The study of various microsatellite polymorphisms ruled out false paternity and therefore confirmed that M45I occurred de novo in the paternal germline or in the early development of the patient. Site-directed mutagenesis showed that M45I results in the absence of in vitro alkaline phosphatase activity, suggesting that the mutation is a severe allele. In conclusion, childhood hypophosphatasia in this patient is the result of compound heterozygosity for the moderate mutation E174K and a novel severe de novo mutation M45I.</description><subject>Adolescent</subject><subject>Alkaline Phosphatase - genetics</subject><subject>Biological and medical sciences</subject><subject>Endocrinopathies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Hypophosphatasia - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mutation, Missense</subject><subject>Vertebrates: endocrinology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0L9v1DAYxnELgehR2JiRF5hI8ZvY-TFWB7RIbWEoEpvl2K8VHzk79Zsg9b8npzvRhcmDP3pe6cvYWxAXUIL4tLMXpRCyAKnqZ2wDnVRFA13znG2EKKHomvLXGXtFtBMCpFTVS3YGqm4ARLlhD9shjG5IyfHrxylNQ6JpMLOhYPjnBfmcuOEO-V36k_htIMJIyG-X2cwhRR4inwfk9-vHgsVdijShDT5Yfjn-NmOIyH_8m0R-hRFfsxfejIRvTu85-_n1y_32urj5fvVte3lTWFm2c-F87bypPfpe1dB2RkLnQclOAdRV24nWlYDGoQcJFRpsql42rpeqFaZvuuqcfTjuTjk9LEiz3geyOI4mYlpIQ1MpaEGu8OMR2pyIMno95bA3-VGD0IfEemf1IbE-JF75u9Pu0u_RPeFT0xW8PwFD1ow-m2gDPbm6bpsKDkPV0WF0yea11ZSRSO_SkuNa5v_n_wKkuZXK</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Taillandier, A.</creator><creator>Sallinen, S.-L.</creator><creator>Brun-Heath, I.</creator><creator>De Mazancourt, P.</creator><creator>Serre, J.-L.</creator><creator>Mornet, E.</creator><general>Endocrine Society</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>7QP</scope></search><sort><creationdate>20050401</creationdate><title>Childhood Hypophosphatasia Due to a de Novo Missense Mutation in the Tissue-Nonspecific Alkaline Phosphatase Gene</title><author>Taillandier, A. ; Sallinen, S.-L. ; Brun-Heath, I. ; De Mazancourt, P. ; Serre, J.-L. ; Mornet, E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-df6dfa6fefb56189a419f1549511638908d21eadef1413eae73b47db4580ab793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adolescent</topic><topic>Alkaline Phosphatase - genetics</topic><topic>Biological and medical sciences</topic><topic>Endocrinopathies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Hypophosphatasia - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mutation, Missense</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taillandier, A.</creatorcontrib><creatorcontrib>Sallinen, S.-L.</creatorcontrib><creatorcontrib>Brun-Heath, I.</creatorcontrib><creatorcontrib>De Mazancourt, P.</creatorcontrib><creatorcontrib>Serre, J.-L.</creatorcontrib><creatorcontrib>Mornet, E.</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>Calcium & Calcified Tissue Abstracts</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taillandier, A.</au><au>Sallinen, S.-L.</au><au>Brun-Heath, I.</au><au>De Mazancourt, P.</au><au>Serre, J.-L.</au><au>Mornet, E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Childhood Hypophosphatasia Due to a de Novo Missense Mutation in the Tissue-Nonspecific Alkaline Phosphatase Gene</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>90</volume><issue>4</issue><spage>2436</spage><epage>2439</epage><pages>2436-2439</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Hypophosphatasia is an inherited disorder due to mutations in the bone alkaline phosphatase (ALPL) gene. We report here a patient with childhood hypophosphatasia diagnosed at 1.4 yr because of pectus excavatum, large anterior fontanel, rachitic skeletal changes, and low serum alkaline phosphatase. Sequencing of the ALPL gene produced evidence of two distinct missense mutations, E174K (c.571G>A), of maternal origin, and a de novo mutation, M45I (c.186G>C). The study of various microsatellite polymorphisms ruled out false paternity and therefore confirmed that M45I occurred de novo in the paternal germline or in the early development of the patient. Site-directed mutagenesis showed that M45I results in the absence of in vitro alkaline phosphatase activity, suggesting that the mutation is a severe allele. In conclusion, childhood hypophosphatasia in this patient is the result of compound heterozygosity for the moderate mutation E174K and a novel severe de novo mutation M45I.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>15671102</pmid><doi>10.1210/jc.2004-1456</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2005-04, Vol.90 (4), p.2436-2439 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17351814 |
| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | Adolescent Alkaline Phosphatase - genetics Biological and medical sciences Endocrinopathies Fundamental and applied biological sciences. Psychology Humans Hypophosphatasia - genetics Male Medical sciences Mutation, Missense Vertebrates: endocrinology |
| title | Childhood Hypophosphatasia Due to a de Novo Missense Mutation in the Tissue-Nonspecific Alkaline Phosphatase Gene |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T01%3A15%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Childhood%20Hypophosphatasia%20Due%20to%20a%20de%20Novo%20Missense%20Mutation%20in%20the%20Tissue-Nonspecific%20Alkaline%20Phosphatase%20Gene&rft.jtitle=The%20journal%20of%20clinical%20endocrinology%20and%20metabolism&rft.au=Taillandier,%20A.&rft.date=2005-04-01&rft.volume=90&rft.issue=4&rft.spage=2436&rft.epage=2439&rft.pages=2436-2439&rft.issn=0021-972X&rft.eissn=1945-7197&rft.coden=JCEMAZ&rft_id=info:doi/10.1210/jc.2004-1456&rft_dat=%3Cproquest_cross%3E17351814%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17351814&rft_id=info:pmid/15671102&rfr_iscdi=true |