Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy‐dystroglycanopathy C1

Muscular dystrophy‐dystroglycanopathy (MDDG) is a genetically and clinically heterogeneous group of muscular disorders, characterized by congenital muscular dystrophy or later‐onset limb‐girdle muscular dystrophy accompanied by brain and ocular abnormalities, resulting from aberrant alpha‐dystroglyc...

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Veröffentlicht in:Journal of cellular and molecular medicine 2017-07, Vol.21 (7), p.1388-1393
Hauptverfasser: Hu, Pengzhi, Wu, Song, Yuan, Lamei, Lin, Qiongfen, Zheng, Wen, Xia, Hong, Xu, Hongbo, Guan, Liping, Deng, Hao
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container_issue 7
container_start_page 1388
container_title Journal of cellular and molecular medicine
container_volume 21
creator Hu, Pengzhi
Wu, Song
Yuan, Lamei
Lin, Qiongfen
Zheng, Wen
Xia, Hong
Xu, Hongbo
Guan, Liping
Deng, Hao
description Muscular dystrophy‐dystroglycanopathy (MDDG) is a genetically and clinically heterogeneous group of muscular disorders, characterized by congenital muscular dystrophy or later‐onset limb‐girdle muscular dystrophy accompanied by brain and ocular abnormalities, resulting from aberrant alpha‐dystroglycan glycosylation. Exome sequencing and Sanger sequencing were performed on a six‐generation consanguineous Han Chinese family, members of which had autosomal recessive MDDG. Compound heterozygous mutations, c.1338+1G>A (p.H415Kfs*3) and c.1457G>C (p.W486S, rs746849558), in the protein O‐mannosyltransferase 1 gene (POMT1), were identified as the genetic cause. Patients that exhibited milder MDDG manifested as later‐onset progressive proximal pelvic, shoulder girdle and limb muscle weakness, joint contractures, mental retardation and elevated creatine kinase, without structural brain or ocular abnormalities, were further genetically diagnosed as MDDGC1. The POMT1 gene splice‐site mutation (c.1338+1G>A) which leads to exon 13 skipping and results in a truncated protein may contribute to a severe phenotype, while the allelic missense mutation (p.W486S) may reduce MDDG severity. These findings may expand phenotype and mutation spectrum of the POMT1 gene. Clinical diagnosis supplemented with molecular screening may result in more accurate diagnoses of, prognoses for, and improved genetic counselling for this disease.
doi_str_mv 10.1111/jcmm.13068
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Exome sequencing and Sanger sequencing were performed on a six‐generation consanguineous Han Chinese family, members of which had autosomal recessive MDDG. Compound heterozygous mutations, c.1338+1G&gt;A (p.H415Kfs*3) and c.1457G&gt;C (p.W486S, rs746849558), in the protein O‐mannosyltransferase 1 gene (POMT1), were identified as the genetic cause. Patients that exhibited milder MDDG manifested as later‐onset progressive proximal pelvic, shoulder girdle and limb muscle weakness, joint contractures, mental retardation and elevated creatine kinase, without structural brain or ocular abnormalities, were further genetically diagnosed as MDDGC1. The POMT1 gene splice‐site mutation (c.1338+1G&gt;A) which leads to exon 13 skipping and results in a truncated protein may contribute to a severe phenotype, while the allelic missense mutation (p.W486S) may reduce MDDG severity. These findings may expand phenotype and mutation spectrum of the POMT1 gene. 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Exome sequencing and Sanger sequencing were performed on a six‐generation consanguineous Han Chinese family, members of which had autosomal recessive MDDG. Compound heterozygous mutations, c.1338+1G&gt;A (p.H415Kfs*3) and c.1457G&gt;C (p.W486S, rs746849558), in the protein O‐mannosyltransferase 1 gene (POMT1), were identified as the genetic cause. Patients that exhibited milder MDDG manifested as later‐onset progressive proximal pelvic, shoulder girdle and limb muscle weakness, joint contractures, mental retardation and elevated creatine kinase, without structural brain or ocular abnormalities, were further genetically diagnosed as MDDGC1. The POMT1 gene splice‐site mutation (c.1338+1G&gt;A) which leads to exon 13 skipping and results in a truncated protein may contribute to a severe phenotype, while the allelic missense mutation (p.W486S) may reduce MDDG severity. These findings may expand phenotype and mutation spectrum of the POMT1 gene. Clinical diagnosis supplemented with molecular screening may result in more accurate diagnoses of, prognoses for, and improved genetic counselling for this disease.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Consanguinity</subject><subject>DNA Mutational Analysis</subject><subject>Exome - genetics</subject><subject>exome sequencing</subject><subject>Female</subject><subject>Genetic Counseling</subject><subject>genetic counselling</subject><subject>Genetic Predisposition to Disease</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Male</subject><subject>Mannosyltransferases - genetics</subject><subject>Middle Aged</subject><subject>muscular dystrophy‐dystroglycanopathy</subject><subject>Mutation</subject><subject>Original</subject><subject>Phenotype</subject><subject>POMT1 gene</subject><subject>RNA Splice Sites - genetics</subject><subject>Walker-Warburg Syndrome - genetics</subject><subject>Walker-Warburg Syndrome - physiopathology</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNpVUcFu1DAUtBCIlsKFD0A-ctlix3bsvSChqBRQV-2hnC3Hedm4suMQO62CVIlP4Bv7JU27S0Xf5Y305s1IMwi9p-SYLvPpyoZwTBkp1Qt0SIUqVnzN-Ms9poqpA_QmpStCWEnZ-jU6KBQVshDyEN1WMQxx6hvcQYYx_p63cUr44nxzSXGYssku9gm7Hhtcda6HBLg1wfkZ37jcYTPlmGIwHo9gISV3DctbspM3I27mlMc4dPPdn787vPWzNX0cTO5mXNG36FVrfIJ3-32Efn49uay-rc7OT79XX85WA-NcrazgIKUCq2xbGyYYMXVj2rogJQPVlq1UjIGltbRtycuSry0RxFrTQtkUTcOO0Oed7jDVARoLfR6N18PoghlnHY3Tzy-96_Q2XmvBlVwXYhH4uBcY468JUtbBJQvemx6WvDRVpRCMF1Iu1A__ez2Z_Mt8IdAd4cZ5mJ_ulOiHNvVDm_qxTf2j2mweEbsHCaCZGA</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Hu, Pengzhi</creator><creator>Wu, Song</creator><creator>Yuan, Lamei</creator><creator>Lin, Qiongfen</creator><creator>Zheng, Wen</creator><creator>Xia, Hong</creator><creator>Xu, Hongbo</creator><creator>Guan, Liping</creator><creator>Deng, Hao</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201707</creationdate><title>Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy‐dystroglycanopathy C1</title><author>Hu, Pengzhi ; Wu, Song ; Yuan, Lamei ; Lin, Qiongfen ; Zheng, Wen ; Xia, Hong ; Xu, Hongbo ; Guan, Liping ; Deng, Hao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3448-c54e778ec8cfba3530abdafb2063e8f6f7833ec1b7cf646649c050ccafe6d2dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Consanguinity</topic><topic>DNA Mutational Analysis</topic><topic>Exome - genetics</topic><topic>exome sequencing</topic><topic>Female</topic><topic>Genetic Counseling</topic><topic>genetic counselling</topic><topic>Genetic Predisposition to Disease</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Male</topic><topic>Mannosyltransferases - genetics</topic><topic>Middle Aged</topic><topic>muscular dystrophy‐dystroglycanopathy</topic><topic>Mutation</topic><topic>Original</topic><topic>Phenotype</topic><topic>POMT1 gene</topic><topic>RNA Splice Sites - genetics</topic><topic>Walker-Warburg Syndrome - genetics</topic><topic>Walker-Warburg Syndrome - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Pengzhi</creatorcontrib><creatorcontrib>Wu, Song</creatorcontrib><creatorcontrib>Yuan, Lamei</creatorcontrib><creatorcontrib>Lin, Qiongfen</creatorcontrib><creatorcontrib>Zheng, Wen</creatorcontrib><creatorcontrib>Xia, Hong</creatorcontrib><creatorcontrib>Xu, Hongbo</creatorcontrib><creatorcontrib>Guan, Liping</creatorcontrib><creatorcontrib>Deng, Hao</creatorcontrib><collection>Wiley-Blackwell Open Access Titles(OpenAccess)</collection><collection>Wiley Online Library Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Pengzhi</au><au>Wu, Song</au><au>Yuan, Lamei</au><au>Lin, Qiongfen</au><au>Zheng, Wen</au><au>Xia, Hong</au><au>Xu, Hongbo</au><au>Guan, Liping</au><au>Deng, Hao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy‐dystroglycanopathy C1</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2017-07</date><risdate>2017</risdate><volume>21</volume><issue>7</issue><spage>1388</spage><epage>1393</epage><pages>1388-1393</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Muscular dystrophy‐dystroglycanopathy (MDDG) is a genetically and clinically heterogeneous group of muscular disorders, characterized by congenital muscular dystrophy or later‐onset limb‐girdle muscular dystrophy accompanied by brain and ocular abnormalities, resulting from aberrant alpha‐dystroglycan glycosylation. Exome sequencing and Sanger sequencing were performed on a six‐generation consanguineous Han Chinese family, members of which had autosomal recessive MDDG. Compound heterozygous mutations, c.1338+1G&gt;A (p.H415Kfs*3) and c.1457G&gt;C (p.W486S, rs746849558), in the protein O‐mannosyltransferase 1 gene (POMT1), were identified as the genetic cause. Patients that exhibited milder MDDG manifested as later‐onset progressive proximal pelvic, shoulder girdle and limb muscle weakness, joint contractures, mental retardation and elevated creatine kinase, without structural brain or ocular abnormalities, were further genetically diagnosed as MDDGC1. The POMT1 gene splice‐site mutation (c.1338+1G&gt;A) which leads to exon 13 skipping and results in a truncated protein may contribute to a severe phenotype, while the allelic missense mutation (p.W486S) may reduce MDDG severity. These findings may expand phenotype and mutation spectrum of the POMT1 gene. Clinical diagnosis supplemented with molecular screening may result in more accurate diagnoses of, prognoses for, and improved genetic counselling for this disease.</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>28157257</pmid><doi>10.1111/jcmm.13068</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Consanguinity
DNA Mutational Analysis
Exome - genetics
exome sequencing
Female
Genetic Counseling
genetic counselling
Genetic Predisposition to Disease
Heterozygote
Humans
Male
Mannosyltransferases - genetics
Middle Aged
muscular dystrophy‐dystroglycanopathy
Mutation
Original
Phenotype
POMT1 gene
RNA Splice Sites - genetics
Walker-Warburg Syndrome - genetics
Walker-Warburg Syndrome - physiopathology
title Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy‐dystroglycanopathy C1
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