부산대학교 도서관

Background and purpose: Muscular A‐type lamin‐interacting protein (MLIP) is most abundantly expressed in cardiac and skeletal muscle. In vitro 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 MLIP gene with human disease in five individuals from two unrelated pedigrees. Methods: Clinical evaluation and exome sequencing were performed in two unrelated families with elevated creatine kinase level. Results: Family 1. A 6‐year‐old girl born to consanguineous parents of Arab‐Muslim origin presented with myalgia, early fatigue after mild‐to‐moderate physical exertion, and elevated creatine kinase levels up to 16,000 U/L. Exome sequencing revealed a novel homozygous nonsense variant, c.2530C>T; p.Arg844Ter, in the MLIP gene. Family 2. 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 MLIP variant c.1825A>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. Conclusions: Our findings suggest that biallelic truncating variants in MLIP result in myopathy characterized by hyperCKemia. Moreover, these cases of MLIP‐related disease may indicate that at least in some instances this condition is associated with muscle decompensation and fatigability during low‐to‐moderate intensity muscle exertion as well as possible cardiac involvement. [ABSTRACT FROM AUTHOR]