{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:30:50Z","timestamp":1784867450606,"version":"3.55.0"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Muscular A\u2010type lamin\u2010interacting protein (MLIP) is most abundantly expressed in cardiac and skeletal muscle. <jats:italic>In vitro<\/jats:italic> and animal studies have shown its regulatory role in myoblast differentiation and in organization of myonuclear positioning in skeletal muscle, as well as in cardiomyocyte adaptation and cardiomyopathy. We report the association of biallelic truncating variation in the <jats:italic>MLIP<\/jats:italic> gene with human disease in five individuals from two unrelated pedigrees.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical evaluation and exome sequencing were performed in two unrelated families with elevated creatine kinase level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Family 1<\/jats:italic>. A 6\u2010year\u2010old girl born to consanguineous parents of Arab\u2010Muslim origin presented with myalgia, early fatigue after mild\u2010to\u2010moderate physical exertion, and elevated creatine kinase levels up to 16,000 U\/L. Exome sequencing revealed a novel homozygous nonsense variant, c.2530C&gt;T; p.Arg844Ter, in the\u00a0<jats:italic>MLIP<\/jats:italic> gene. <jats:italic>Family 2<\/jats:italic>. Three individuals from two distantly related families of Old Order Amish ancestry presented with elevated creatine kinase levels, one of whom also presented with abnormal electrocardiography results. On exome sequencing, all showed homozygosity for a novel nonsense <jats:italic>MLIP<\/jats:italic> variant c.1825A&gt;T; p.Lys609Ter. Another individual from this pedigree, who had sinus arrhythmia and for whom creatine kinase level was not available, was also homozygous for this variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that biallelic truncating variants in <jats:italic>MLIP<\/jats:italic> result in myopathy characterized by hyperCKemia. Moreover, these cases of <jats:italic>MLIP<\/jats:italic>\u2010related disease may indicate that at least in some instances this condition is associated with muscle decompensation and fatigability during low\u2010to\u2010moderate intensity muscle exertion as well as possible cardiac involvement.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15218","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T08:55:47Z","timestamp":1640163347000},"page":"1174-1180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Biallelic truncating variants in the muscular A\u2010type lamin\u2010interacting protein (<i>MLIP<\/i>) gene cause myopathy with hyperCKemia"],"prefix":"10.1111","volume":"29","author":[{"given":"Liat","family":"Salzer\u2010Sheelo","sequence":"first","affiliation":[{"name":"Raphael Recanati Genetics Institute Rabin Medical Center, Beilinson Hospital Petah Tikva 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Hospital Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Lev\u2010El Halabi","sequence":"additional","affiliation":[{"name":"Raphael Recanati Genetics Institute Rabin Medical Center, Beilinson Hospital Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Daue","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pola","family":"Smirin\u2010Yosef","sequence":"additional","affiliation":[{"name":"Genomic Bioinformatics Laboratory, Department of Molecular Biology Ariel University Ariel Israel"},{"name":"Felsenstein Medical Research Center Rabin Medical Center Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristopher V.","family":"Van 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