We report a second family with autosomal dominant TNPO3/transportinopathy presenting with congenital or early-onset myopathy and slow progression, causing proximal and less pronounced distal muscle weakness. Patients of this Swedish family had clinical examinations, muscle MRI and EMG. Muscle biopsies were used for histopathological and protein expression studies, and TNPO3 constructs were used to study the effect of the mutations in transfected cells. By using the MYOcap targeted exome sequencing gene panel, we identified a novel heterozygous mutation, c.2757delC, in the last part of the Transportin-3/TNPO3 gene in the affected family members. The mutation causes an almost identical frameshift affecting the stop codon and elongating the C-term protein product of the TNPO3 transcript as was previously reported in the first large Spanish-Italian LGMD1F kindred. TNPO3 belongs to the importin beta superfamily, facilitating the nuclear import of Ser/Arg-rich (SR) proteins. TNPO3 plays a role in HIV infection, however, little is known of its normal functions in muscle. We found that the TNPO3 protein was increased in the patient muscle, and accumulated in the subsarcolemmal and perinuclear areas in muscle biopsy. One of the cargo proteins, the splicing factor SRRM2 was normally located in the nucleus, whereas RBM4 showed perinuclear accumulation. In addition, transiently transfected mutant TNPO3 constructs failed to localize to cytoplasmic annulate lamellae pore complexes in cultured cells. We report the clinical, molecular genetic and histopathological features of the second transportinopathy family. The variability of the clinical phenotype together with histopathological findings suggest that several molecular pathways may be involved in the disease pathomechanism, such as nucleo-cytoplasmic shuttling, protein aggregation, and defective protein turnover.