Biallelic Mutations in MYPN, Encoding Myopalladin, Are Associated with Childhood-Onset, Slowly Progressive Nemaline Myopathy.

Nemaline myopathy (NM) is a common form of congenital nondystrophic skeletal muscle disease characterized by muscular weakness of proximal dominance, hypotonia, and respiratory insufficiency but typically not cardiac dysfunction. Wide variation in severity has been reported. Intranuclear rod myopathy is a subtype of NM in which rod-like bodies are seen in the nucleus, and it often manifests as a severe phenotype. Although ten mutant genes are currently known to be associated with NM, only ACTA1 is associated with intranuclear rod myopathy. In addition, the genetic cause remains unclear in approximately 25%-30% of individuals with NM. We performed whole-exome sequencing on individuals with histologically confirmed but genetically unsolved NM. Our study included individuals with milder, later-onset NM and identified biallelic loss-of-function mutations in myopalladin (MYPN) in four families. Encoded MYPN is a sarcomeric protein exclusively localized in striated muscle in humans. Individuals with identified MYPN mutations in all four of these families have relatively mild, childhood- to adult-onset NM with slowly progressive muscle weakness. Walking difficulties were recognized around their forties. Decreased respiratory function, cardiac involvement, and intranuclear rods in biopsied muscle were observed in two individuals. MYPN was localized at the Z-line in control skeletal muscles but was absent from affected individuals. Homozygous knockin mice with a nonsense mutation in Mypn showed Z-streaming and nemaline-like bodies adjacent to a disorganized Z-line on electron microscopy, recapitulating the disease. Our results suggest that MYPN screening should be considered in individuals with mild NM, especially when cardiac problems or intranuclear rods are present.

Performance evaluation of platelet counting by novel fluorescent dye staining in the XN-series automated hematology analyzers.

BACKGROUND: Conventional automated hematology analyzers have limitations in platelet measurements such as poor accuracy and precision in the low count range and interference by nonplatelet particles. In order to improve it, the newly developed XN-Series automated hematology analyzers (Sysmex Corporation, Kobe, Japan) have been installed with a new dedicated channel for platelet analysis (PLT-F), which is based on a fluorescence flow cytometry method with uses of a novel fluorescent dye specifically staining platelets. We evaluated the basic performance of this new PLT-F channel. METHODS: Basic performance of the PLT-F channel in within-run reproducibility and assay linearity was studied using standard methods. Correlation was studied between PLT-F and a conventional automated hematology analyzer (XE-2100) and immunoplatelet analysis using anti-CD61 monoclonal antibody (Cell-Dyn Sapphire; Abbott Laboratories). The assay interference by nonplatelet particles such as fragmented red and white blood cells was evaluated by using clinical samples, respectively, from burn injury and acute leukemia. RESULTS: Basic performance of the PLT-F platelet counting was satisfactory in within-run reproducibility, linearity and correlation with the conventional analyzer. The correlation was satisfactory also with the immunoplatelet analysis, even for samples from a patient with burn injury, and those with white blood cell fragments displayed, platelet abnormal flag and low platelet counts (<50 × 10(9)/l). CONCLUSION: The platelet counting performance of the PLT-F channel of the XN Series had improved accuracy and precision in the low range and in abnormal samples, avoiding the interference by nonplatelet particles.

Clinical and pathological features of B-cell non-Hodgkin lymphomas lacking the surface expression of immunoglobulin light chains.

BACKGROUND: The flow cytometric analysis of surface immunoglobulin light chains (sIgL) is used as a simple method for evaluating monoclonal B-cell proliferation. However, the sIgL expression, κ or λ, is occasionally undetectable in cases with B-cell non-Hodgkin lymphomas (B-NHL). The purpose of this study was to investigate the clinical and pathological characteristics of these B-NHL cases. METHODS: We retrospectively analyzed 50 cases with previously untreated sIgL-negative B-NHL. All of these cases had been diagnosed at Tokai University Hospital between January 2001 and February 2011. Their medical charts were reviewed. RESULTS: These cases had several clinical features: diffuse large B-cell lymphoma (DLBCL) (72%), a high serum lactate dehydrogenase level (66%), clinical stage III and IV (68%), and complex karyotypes (58%). Seven out of eight evaluated patients (87%) did not express cytoplasmic IgL, and the DNA rearrangement pattern of IgL showed diversity in 10 analyzed patients. The 5-year event-free survival of all the sIgL-negative B-NHL cases was significantly better with rituximab-containing chemotherapies in comparison to the regimens without it (57.9% vs. 17.9%, p=0.0207), although there was no statistical significance when the DLBCL cases were analyzed (56.6% vs. 22.2%, p=0.1530). CONCLUSIONS: These findings suggest that sIgL-negative B-NHL cases predominantly developed DLBCL in advanced disease, but were heterogeneous at the molecular level.

[Intractable Neurological Disease].

Subacute intractable neurological diseases sometimes require patients to make various choices in life without accepting the disease. Therefore, doctors need to be diagnose these diseases early. However, in clinical settings, diagnosis is often sought only from the localized history and symptoms and not the overall picture of the disease. In addition, there are many findings that are difficult to interpret, and depending on the combination of findings, the diagnostic criteria or guidelines may be met. As a result, the disease fits only seemingly to the findings. Therefore, I would like to urge physicians to be aware of pitfalls by referring to the cases refferred to our neurology department for us to assess them.

Two Japanese LGMDR25 patients with a biallelic recurrent nonsense variant of BVES.

We report two Japanese patients with autosomal recessive limb-girdle muscular dystrophy type R25 (LGMDR25), harboring a novel recurrent homozygous nonsense variant of BVES. Muscle symptoms manifested from childhood to adulthood, initiated in the proximal or distal muscles of the lower limbs, and displayed asymmetric muscle involvement. Similar to the patients in previous reports, these patients also lost ambulation in late middle age. The posterior compartment of the lower limb muscles (biceps femoris, adductor magnus, gastrocnemius, and soleus) was preferentially affected as was the paraspinal muscle. Muscles in the anterior compartment of the thigh were affected in more advanced stages. Both patients had symptomatic atrioventricular block. The POPDC1 protein was undetectable in the muscles of the patients. As observed by transmission electron microscopy, one of the patient samples had fewer caveolae along the sarcolemma than a control sample.

Traumatic axial dislocation of the carpus: a case report of transscaphoid pericapitate transhamate axial dislocation.

Traumatic axial dislocation of the carpus in a 20-year-old man is described. This injury was accompanied by a crushing injury to the hand. The disruption pattern was different from those of previously reported cases. Despite the restoration of painless wrist motion postoperatively, grip strength remained below normal. Early accurate reduction, fixation, and range of motion (ROM) exercise are the treatment of choice in such complex injuries.