A familial case of B-cell expansion with NF-κB and T-cell anergy caused by a G123D heterozygous missense mutation in the CARD11 gene.

B-cell expansion with NF-κB (nuclear factor-kappa B) and T-cell anergy (BENTA) is a rare congenital lymphoproliferative disorder caused by germline gain-of-function mutations in the CARD11 gene. We herein report a familial case of BENTA due to a G123D heterozygous missense mutation in CARD11 inherited by a male from his mother. The mother's clinical course was characterized by polyarthritis and encephalitis in young adulthood, suggesting that autoimmune-like manifestations can occur in BENTA. The B-cell lymphocytosis and splenomegaly seen in her child have been managed with prednisolone and tacrolimus. Further investigations are needed to evaluate the efficacy of calcineurin inhibitors for BENTA.

Siblings with congenital thrombotic thrombocytopenic purpura.

Congenital thrombotic thrombocytopenic purpura (TTP) is a rare hereditary deficiency of ADAMTS13 (von Willebrand factor-cleaving protease) characterized by thrombocytopenia and microangiopathic hemolytic anemia. The spectrum of the clinical phenotype is wide, ranging from asymptomatic episodes of thrombocytopenia to life-threatening multiorgan failure. Reportedly, some patients develop isolated thrombocytopenia during childhood. We herein report sibling cases of congenital TTP. An 11-year-old boy with thrombocytopenia accompanied by influenza virus infection was referred to our hospital. He had a history of severe neonatal jaundice. His 15-year-old brother also had recurrent thrombocytopenia with approximately 10 episodes of recurrence since 3 years of age. Their ADAMTS13 activities were low and ADAMTS13 inhibitors were negative, and a gene analysis confirmed the diagnosis of congenital TTP. Notably, congenital TTP should be included in the differential diagnosis, and it is essential to determine the ADAMTS13 activity for pediatric patients with thrombocytopenia of unknown etiology.

A Neonatal Case of Glial Choristoma of the Tongue Causing Airway Obstruction.

Glial choristoma is considered to be a type of brain heterotopia consisting of ectopic central nervous tissue. We herein report a neonate with glial choristoma of the tongue who developed respiratory distress due to airway obstruction. A male neonate presented with respiratory distress due to a soft mass on the midline region of the dorsal tongue base at birth. He was intubated using a flexible fiberoptic nasopharyngoscope. MRI showed a well-circumscribed mass measuring 25 × 23 × 27 mm in size in the same region. A histologic examination confirmed a pathological diagnosis of glial choristoma. He underwent tracheotomy at 22 days of age, and a subtotal resection of the tumor was performed at five months of age. The clinical behavior of oral glial choristoma varies depending on the age at onset as well as the location and size of the mass. The small size of the organ and the narrow operating field hamper the surgical approach in neonates. The optimal therapeutic strategy for neonatal cases of glial choristoma should thus be determined based on the condition of each individual patient.

Fusion PCR generated Japanese encephalitis virus/dengue 4 virus chimera exhibits lack of neuroinvasiveness, attenuated neurovirulence, and a dual-flavi immune response in mice.

The first flavivirus chimera encoding dengue 4 virus (D4) PrM and E structural proteins in a Japanese encephalitis virus (JEV) backbone was successfully generated using the long-PCR based cDNA-fragment stitching (LPCRcFS) technique, demonstrating the technique's applicability for rapid preparation of flavivirus chimeras. The JEV/D4 chimera multiplied at levels equal to JEV and D4 in the mosquito cell line C6/36, while in a mouse neuronal cell line (N2a) JEV replicated efficiently, but JEV/D4 and D4 did not. In mouse challenge experiments, JEV/D4 showed a lack of neuroinvasiveness similar to D4 when inoculated intraperitoneally, but demonstrated attenuated neurovirulence (LD50=3.17 x 10(4) f.f.u.) when inoculated intracranially. It was also noted that mice receiving intraperitoneal challenge with JEV/D4 possessed D4-specific neutralization antibody and in addition clearly showed resistance to JEV intraperitoneal challenge (at 100 x LD50). This suggests that immunity to anti-JEV non-structural protein(s) offers protection against JEV infection in vivo. Dengue secondary infection was also simulated by challenging mice pre-immunized with dengue 2 virus, with D4 or JEV/D4. Mice showed higher secondary antibody response to challenge with JEV/D4 than to D4, at 210,000 and 37,000 averaged ELISA units, respectively. Taken together, aside from demonstrating the LPCRcFS technique, it could be concluded that the PrM and E proteins are the major determinant of neuroinvasiveness for JEV. It is also expected that the JEV/D4 chimera with its pathogenicity in mice and atypical immune profile, could have applications in dengue prophylactic research, in vivo efficacy assessment of dengue vaccines and development of animal research on models of dengue secondary infection.