Leucine-485 deletion variant of BRAF may exhibit the severe end of the clinical spectrum of CFC syndrome.

The genotype-phenotype correlation in BRAF variant in cardio-facio-cutaneous (CFC) syndrome is not clearly defined. Here we report a case with a severe clinical phenotype and a novel BRAF variant, p.Leu485del. The present case showed severe intellectual disability, impaired awareness, hyperekplexia, involuntary movements, early onset refractory seizures, and delayed myelination on brain magnetic resonance imaging as well as a polycystic and dysplastic kidney, which are previously unreported anomalies in CFC or RAS/mitogen-activated protein kinase syndromes related to BRAF variant. CFC syndrome, especially caused by BRAF variant, should be included in the differential diagnosis of patients with developmental and epileptic encephalopathies and hyperekplexia. Furthermore, we need to keep in mind that missense variants or the deletion of Leucine-485 may be associated with severe symptoms.

Genomic analysis identifies masqueraders of full-term cerebral palsy.

OBJECTIVE: Cerebral palsy is a common, heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent studies have suggested genetic diseases can be misdiagnosed as cerebral palsy. We hypothesized that two simple criteria, that is, full-term births and nonspecific brain MRI findings, are keys to extracting masqueraders among cerebral palsy cases due to the following: (1) preterm infants are susceptible to multiple environmental factors and therefore demonstrate an increased risk of cerebral palsy and (2) brain MRI assessment is essential for excluding environmental causes and other particular disorders. METHODS: A total of 107 patients-all full-term births-without specific findings on brain MRI were identified among 897 patients diagnosed with cerebral palsy who were followed at our center. DNA samples were available for 17 of the 107 cases for trio whole-exome sequencing and array comparative genomic hybridization. We prioritized variants in genes known to be relevant in neurodevelopmental diseases and evaluated their pathogenicity according to the American College of Medical Genetics guidelines. RESULTS: Pathogenic/likely pathogenic candidate variants were identified in 9 of 17 cases (52.9%) within eight genes: CTNNB1,CYP2U1,SPAST,GNAO1,CACNA1A,AMPD2,STXBP1, and SCN2A. Five identified variants had previously been reported. No pathogenic copy number variations were identified. The AMPD2 missense variant and the splice-site variants in CTNNB1 and AMPD2 were validated by in vitro functional experiments. INTERPRETATION: The high rate of detecting causative genetic variants (52.9%) suggests that patients diagnosed with cerebral palsy in full-term births without specific MRI findings may include genetic diseases masquerading as cerebral palsy.

Geographical distribution of Metagonimus yokogawai and M. miyatai in Shizuoka Prefecture, Japan, and their site preferences in the sweetfish, Plecoglossus altivelis, and hamsters.

Sweetfish, Plecoglossus altivelis, obtained from 18 rivers in Shizuoka Prefecture were examined for metacercarial infection of 2 flukes, Metagonimus yokogawai and Metagonimus miyatai. The infection rate and density of metacercariae in the fish were higher in eastern and western regions than in central region of the prefecture. After infection of hamsters with metacercariae derived from the scale, 98.7% of the adult worms obtained from the intestine was found to be M. miyatai. Conversely, from infection with metacercariae from the flesh, 90.0% of the worms was M. yokogawai. Since the worms had no exclusivity in the tissues, we conclude that the flukes have location preference with the former primarily preferring the scale, and the latter the flesh. Fish from two rivers located in adjacent areas in the western region had relatively a higher ratio of M. yokogawai in the scale relative to other rivers, suggesting an intraspecific genetic variation due to geographical isolation. On examination of adult worms in the hamster's intestine, M. yokogawai was mainly located towards the anterior part of the intestine, unlike M. miyatai, suggesting that in mammalian host too, the parasites have site preference.

Transient Creatine Kinase Elevation Followed by Hypocomplementemia in a Case of Rotavirus Myositis.

We report an infant case of rotavirus myositis, a rare complication of rotavirus infection. Complement levels of the patient were normal when serum creatine kinase (CK) level was at its peak and then decreased when the CK level became normalized. In a previous case report of rotavirus myositis, transient decrease of serum albumin, immunoglobulin, and complement levels was reported. The authors speculated that intravascular complement activation was caused by rotavirus and resulted in the pathogenesis of myositis, although complement levels at onset were not measured by the authors. In this report, however, we demonstrate that the complement activation of our patient is a result of, rather than the cause of, skeletal muscle damage.

A case of acute cerebellitis with a unique sequential change on magnetic resonance imaging.

BACKGROUND: Acute cerebellitis with unilateral onset is rare, and magnetic resonance imaging (MRI) is a useful method for demonstrating cerebellar involvement. PATIENT: We report a 12-year-old girl with acute cerebellitis with a unique sequential change on her MRI. RESULTS: The patient's brain MRI first revealed cortical lesions mainly in the right cerebellar hemisphere. These subsequently disappeared, and at the same time, new lesions appeared in the opposite cerebellar hemisphere. All the lesions were confined to gray matter in the cerebellum and were isotense on diffusion-weighted imaging and had high signal intensity on the apparent diffusion coefficient map, consistent with the characteristic of vasogenic edema. CONCLUSION: The sequential MRI demonstrates conversion of hemicerebellitis to bilateral cerebellitis during subacute phase, and vasogenic edema might be contributing to the pathogenesis of acute cerebellitis in this patient.

Structural changes of cell wall mannans of Candida guilliermondii IFO 10279 strain cells cultured at high temperature.

The morphology, structure, and antigenicity of the cells and the cell wall mannans of the Candida guilliermondii IFO 10279 strain cultivated at 33 and 34 degrees C for 48 h in yeast extract-added Sabouraud liquid medium (YSLM) were compared with those cultivated at 27 degrees C and 33 degrees C and then at 27 degrees C (33-27 degrees C). This strain showed little growth at higher than 35 degrees C. The density of the yeast formed cells decreased, with dry weights of about 50% at 33 and 34 degrees C, and only the cells at 34 degrees C revealed a failure of cytokinesis. The structure of the mannans revealed by (1)H-NMR analysis that the mannans obtained at both 33 and 34 degrees C had drastically decreased two consecutive beta-1,2-linked mannopyranose units at the nonreducing terminal of the alpha-linked oligosaccharides and increased one beta-1,2-linked mannopyranose unit at the nonreducing terminal attached to the alpha-1,3-linked mannose unit and the non-reducing terminal alpha-1,3- and alpha-1,2-linked mannopyranose units. The enzyme-linked immunosorbent assay (ELISA) showed that the mannans obtained at 33 and 34 degrees C had decreased reactivity against the factor serum 9 and increased its reactivity against the factor serum 4, in the commercially available factor serum kit "Candida Check".