Kayman-Kurekci G.Talim, B.Korkusuz P.Sayar, N.Sarioglu, T.Oncel I.Sharafi P.Gundesli H.Balci-Hayta, B.Purali, N.Serdaroglu-Oflazer P.Topaloglu H.Dincer P.2016-02-082016-02-0820140960-8966http://hdl.handle.net/11693/26568We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A- and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle. © 2014 Elsevier B.V.EnglishLAP1Muscular dystrophyMyopathyTOR1AIP1lamin Alamin Blamina associated polypeptide 1Bmembrane proteinunclassified drugcarrier proteinLAP1B protein, humanmembrane proteinmessenger RNAnuclear proteinTOR1AIP2 protein, humanarticlebinding affinitybinding sitecase reportclinical featurecontrolled studydisease activitydisease associationechographyfemaleframeshift mutationgenegene functiongene identificationgene locationgene mappinggene mutationgenetic associationhistopathologyhumanhuman tissuemalemolecular dynamicsmolecular pathologymuscle biopsymuscle diseasemuscular dystrophynuclear envelopathyphenotypepriority journalpromoter regionprotein bindingprotein determinationprotein expressionprotein functionprotein localizationsequence analysisstop codontorsin A interacting protein 1 genetransmission electron microscopyadolescentadultamino acid sequencecell nucleus membranefamilyfluorescent antibody techniquegeneticsmetabolismmolecular geneticsmuscular dystrophynucleotide sequencepathologypedigreesarcomereskeletal muscleultrastructureAdolescentAdultAmino Acid SequenceCarrier ProteinsDNA Mutational AnalysisFamilyFemaleFluorescent Antibody TechniqueFrameshift MutationHumansMaleMembrane ProteinsMicroscopy, Electron, TransmissionMolecular Sequence DataMuscle Fibers, SkeletalMuscular DystrophiesNuclear EnvelopeNuclear ProteinsPedigreeRNA, MessengerSarcomeresArticle10.1016/j.nmd.2014.04.007