Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in the Japanese population, is characterized by congenital muscular dystrophy in combination with cortical dysgenesis (micropolygyria). Recently, we identified, on chromosome 9q31, the gene responsible for FCMD, which encodes a novel 461 amino acid protein which we have termed fukutin. Most FCMD-bearing chromosomes examined to date (87%) have been derived from a single ancestral founder, whose mutation consisted of a 3 kb retrotransposal insertion in the 3' non-coding region of the fukutin gene. FCMD is the first human disease known to be caused primarily by an ancient retrotransposal integration. We under-took a systematic analysis of the FCMD gene in 107 unrelated patients, and identified four novel non-founder mutations in five of them: one missense, one nonsense, one L1 insertion and a 1 bp insertion. The frequency of severe phenotypes, including Walker-Walberg syndrome-like manifestations such as hydrocephalus and microphthalmia, was significantly higher among probands who were compound heterozygotes carrying a point mutation on one allele and the founder mutation on the other, than it was among probands who were homozygous for the 3 kb retrotransposon. Remarkably, we detected no FCMD patients with non-founder (point) mutations on both alleles of the gene, and suggest that such cases might be embryonic-lethal. This could explain why few FCMD cases are reported in non-Japanese populations. Our results provided strong evidence that loss of function of fukutin is the major cause of FCMD, and appeared to shed some light on the mechanism responsible for the broad clinical spectrum seen in this disease.

Objective:To report the distinctive clinical features of cryptogenic new-onset refractory status epilepticus (C-NORSE) and the C-NORSE score based on initial clinical assessments.Methods:A retrospective study was conducted for 136 patients with clinically suspected autoimmune encephalitis who underwent testing for autoantibodies to neuronal surface antigens between January 1, 2007, and August 31, 2016. Eleven patients with C-NORSE were identified. Their clinical features were compared with those of 32 patients with anti-NMDA receptor encephalitis (NMDARE).Results:The clinical outcome of 11 patients (median age, 27 years; 7 [64%] women) with C-NORSE was evaluated after a median follow-up of 11 months (range, 6–111 months). Status epilepticus was frequently preceded by fever (10/11 [91%]). Brain MRIs showed symmetric T2/fluid-attenuated inversion recovery hyperintensities (8/11 [73%]) and brain atrophy (9/11 [82%]). Only 2 of the 10 treated patients responded to the first-line immunotherapy, and 4 of the 5 patients treated with IV cyclophosphamide responded to the therapy. The long-term outcome was poor in 8 patients (73%). Compared with 32 patients with NMDARE (median age, 27 years; 24 [75%] women), those with C-NORSE had more frequent prodromal fever, status epilepticus, ventilatory support, and symmetric brain MRI abnormalities, had less frequent involuntary movements, absent psychobehavioral symptoms, CSF oligoclonal bands, or tumor association, and had a worse outcome. The C-NORSE score was higher in patients with C-NORSE than those with NMDARE.Conclusions:Patients with C-NORSE have a spectrum of clinical-immunological features different from those with NMDARE. The C-NORSE score may be useful for discrimination between them. Some patients could respond to immunotherapy.

These findings indicate that laparoscopic hepatectomy avoids the disadvantages of standard hepatectomy for HCC in properly selected patients with cirrhosis and that its minimal invasiveness improves patients' quality of life.

ABSTRACT. We have examined the presence of hemoplasmas, hemotropic mycoplasmas, among domestic cats (Felis catus) in Japan by using a species specific PCR, and found 'Candidatus Mycoplasma turicensis', a recently recognized hemoplasma species. A total of 60 feline blood samples collected in 2004 and 2005 were subjected to PCR amplification for the detection of Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum' and 'Candidatus Mycoplasma turicensis'. Six blood samples collected from domestic cats were found infected with the 'Candidatus M. turicensis'. All of them are also infected with other species of hemoplasmas, M. haemofelis and/or 'Candidatus M. haemominutum'. This is the first to demonstrate 'Candidatus M. turicensis' infections among cat population in Japan. KEY WORDS: feline, hemoplasma, 16S rRNA.

The novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, has spread worldwide from China. There are no case reports from Asia of COVID-19 with facial paralysis and olfactory disturbance. We herein report a case of COVID-19 pneumonia in a Japanese woman who showed facial nerve palsy and olfactory disturbance.

Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer’s disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis. Whole-exome analysis of this family identified a novel missense mutation in BSN. Within the pedigree, the detected BSN mutation was found only in affected individuals. Further genetic analyses were conducted in probands from four other pedigrees with PSP-like syndrome and in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed in databases of healthy subjects were found in four sporadic cases. Western blot analysis of tau following the overexpression of wild-type or mutated BSN revealed the possibility that wild-type BSN reduced tau accumulation, while mutated BSN lost this function. An association between BSN and neurological diseases has not been previously reported. Our results revealed that the neurodegenerative disorder associated with the original proband’s pedigree is a novel tauopathy, differing from known dementia and parkinsonism syndromes, including PSP.

Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in Japan, is characterized by congenital muscular dystrophy associated with brain malformation due to a defect in neuronal migration. Previously, we identified the gene responsible for FCMD, which encodes the fukutin protein. Most FCMD-bearing chromosomes (87%) are derived from a single ancestral founder, who lived 2,000-2,500 years ago and whose mutation consisted of a 3-kb retrotransposal insertion in the 3' non-coding region of the fukutin gene. Here we show, through detailed sequence analysis, that the founder insertion is derived from the SINE-VNTR-Alu (SVA) retroposon. To enable rapid detection of this insertion, we have developed a PCR-based diagnostic method that uses three primers simultaneously. We used this method to investigate the distribution and origin of the founder insertion, screening a total of 4,718 control DNA samples from Japanese and other Northeast Asian populations. Fifteen founder chromosomes were detected among 2,814 Japanese individuals. Heterozygous carriers were found in various regions throughout Japan, with an averaged ratio of 1 in 188. In Korean populations, we detected one carrier in 935 individuals. However, we were unable to detect any heterozygous alleles in 203 Mongolians and 766 Mainland Chinese populations. These data largely rule out the possibility that a single ancestor bearing an insertion-chromosome immigrated to Japan from Korea or Mainland China and appear to confirm that FCMD carriers are rare outside of Japan.

We evaluated the clinical role of the combination of positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and tumor marker CA125, in the detection of recurrence after initial therapy for epithelial ovarian cancer. The indication is the cases that cannot be confirmed the recurrence by conventional imaging modalities. Ninety patients underwent PET and computed tomography, including the measurement of specific tumor markers. FDG-PET confirmed recurrence in 46 patients (51%), and the recurrent site was confirmed by PET alone in 17 (37%). PET had high sensitivity for detecting both intraperitoneal and retroperitoneal metastases (93.9 and 92.9%, respectively). PET imaging was able to detect normal-sized metastases in the lymph nodes in 14 (50%) of the 28 patients with retroperitoneal metastasis. PET could show 87.5% positive rate of recurrent patients with asymptomatic rise of CA125 who had no sign of recurrence by conventional imaging methods. Of the 46 recurrent patients, 41 (89%) had specific elevated titers of CA125 at the first treatment. PET imaging was able to detect recurrence at relatively low titers (a median 68 U/mL) of CA125. In 8 (19.5%) of these 41 patients, recurrence with normal CA125 levels could be confirmed only by PET. The sensitivity of the combination of PET and CA125 was 97.8% with only one false-negative case. The combination of FDG-PET and CA125 titer is useful for the accurate detection of recurrence.