{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:50:12Z","timestamp":1648677012662},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"01","funder":[{"name":"Max Planck Society and by the European Commission Framework Program 7","award":["241995"],"award-info":[{"award-number":["241995"]}]},{"name":"the German Research Foundation","award":["SFB665, SFB1315"],"award-info":[{"award-number":["SFB665, SFB1315"]}]},{"name":"the German Ministry of Education and Research","award":["MD-NET 01GM0302"],"award-info":[{"award-number":["MD-NET 01GM0302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Muscular dystrophy-dystroglycanopathies (MDDG) are a group of genetically heterogeneous autosomal recessive disorders characterized by hypoglycosylation of \u03b1-dystroglycan. Here, we report on two female patients from a consanguineous Lebanese family that presented in early infancy with generalized muscle hypotonia and primary microcephaly. Brain magnetic resonance imaging (MRI) showed different degrees of hypoplasia of the cerebellar vermis and hypoplasia of corpus callosum. Muscle biopsy analyses revealed a muscular dystrophy with reduced expression of \u03b1-dystroglycan and merosin in immunoblot analyses. Homozygosity mapping failed to elucidate the causal mutation due to the accepted notion that, in consanguineous families, homozygote mutations cause disease. However, by applying whole exome sequencing, we identified a novel compound heterozygous POMT1 mutation that segregates with the phenotype and is in line with the clinical presentation. This underscores that a less expected compound heterozygous instead of homozygous mutation in a consanguineous marriage results in a recessive disorder and highlights the growing role of next generation sequencing in neuromuscular disorder diagnostics.<\/jats:p>","DOI":"10.1055\/s-0039-1695787","type":"journal-article","created":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T22:58:18Z","timestamp":1571439498000},"page":"072-075","source":"Crossref","is-referenced-by-count":1,"title":["Just Expect It: Compound Heterozygous Variants of POMT1 in a Consanguineous Family\u2014The Role of Next Generation Sequencing in Neuromuscular Disorders"],"prefix":"10.1055","volume":"51","author":[{"given":"Maja","family":"von der Hagen","sequence":"additional","affiliation":[{"name":"Abteilung Neurop\u00e4diatrie, Universit\u00e4tsklinikum Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena-Luise","family":"Becker","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Klinik f\u00fcr P\u00e4diatrie mit Schwerpunkt Neurologie, Augustenburger Platz 1, Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Sozialp\u00e4diatrisches Zentrum, Augustenburger Platz 1, Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Institut f\u00fcr Zell- und Neurobiologie, Charit\u00e9 Platz 1, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas F.","family":"Wienker","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Molecular Genetics, Ihnestra\u00dfe 63-73, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Smitka","sequence":"additional","affiliation":[{"name":"Abteilung Neurop\u00e4diatrie, Universit\u00e4tsklinikum Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Musante","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Molecular Genetics, Ihnestra\u00dfe 63-73, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Hilger","family":"Ropers","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Molecular Genetics, Ihnestra\u00dfe 63-73, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Huebner","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinder- und Jugendmedizin, Universit\u00e4tsklinikum Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Hu","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Molecular Genetics, Ihnestra\u00dfe 63-73, Berlin, Germany"},{"name":"Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela M.","family":"Kaindl","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Klinik f\u00fcr P\u00e4diatrie mit Schwerpunkt Neurologie, Augustenburger Platz 1, Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Sozialp\u00e4diatrisches Zentrum, Augustenburger Platz 1, Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Institut f\u00fcr Zell- und Neurobiologie, Charit\u00e9 Platz 1, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2019,10,18]]},"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0039-1695787.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:47:30Z","timestamp":1579826850000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0039-1695787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,18]]},"references-count":0,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2020,1,23]]},"published-print":{"date-parts":[[2020,2]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0039-1695787","relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,18]]}}}