Satoko Nakahara

A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures

A naturally occurring mutation of the mass1 (monogenic audiogenic seizure‐susceptible) gene recently has been reported in the Frings mouse strain, which is prone to audiogenic seizures. The human orthologous gene, MASS1, was mapped to chromosome 5q14, for which we previously have reported significant evidence of linkage to febrile seizures (FEB4). We screened for MASS1 mutations in individuals from 48 families with familial febrile seizures and found 25 DNA alterations. None of nine missense polymorphic alleles was significantly associated with febrile seizures; however, a nonsense mutation (S2652X) causing a deletion of the C‐terminal 126 amino acid residues was identified in one family with febrile and afebrile seizures. Our results suggest that a loss‐of‐function mutation in MASS1 might be responsible for the seizure phenotypes, though it is not likely that MASS1 contributed to the cause of febrile seizures in most of our families.

Serum concentrations of insulin, insulin‐like growth factor(IGF)‐I, IGF binding protein (IGFBP)‐1 and ‐3 and growth hormone binding protein in obese children: fasting IGFBP‐1 is suppressed in normoinsulinaemic obese children

Simple obesity is characterized by normal or accelerated growth in the presence of reduced serum levels of GH, whereas its detailed mechanism remains unknown. We, therefore, evaluated interrelationships among serum levels of insulin, IFG‐I, IGF binding protein (IGFBP)‐1 and ‐3 and growth hormone binding protein (GHBP) in prepubertal obese children.

Lack of association of atopy/asthma and the interleukin-4 receptor alpha gene in Japanese.

Susceptibility to the development of atopic diseases is known to involve genetic factors. Several investigators have reported the interleukin‐4 (IL‐4) receptor α gene to be involved in the development of atopy. Recent study has shown that the R allele of a polymorphism in the IL‐4 receptor α chain gene (Q576R) to be associated with atopy.

Serum leptin and insulin concentrations in prepubertal lean, obese and insulin‐dependent diabetes mellitus children

To evaluate the relationship between serum levels of leptin and insulin in prepubertal lean, obese and insulin‐dependent diabetes mellitus (IDDM) children.

Failure to find causal mutations in the GABAA-receptor γ2 subunit (GABRG2) gene in Japanese febrile seizure patients

Recently, mutations in the GABA(A)-receptor gamma2 subunit (GABRG2) gene were identified in two families with generalized epilepsy with febrile seizures plus (GEFS+) and two families with childhood absence epilepsy (CAE) and febrile seizures (FS). We tested the hypothesis that genetic variations in the GABRG2 gene confer susceptibility to FS in the Japanese population. We performed a systematic search for mutations in 94 unrelated Japanese patients with FS and detected six variants (-158C>T, 315C>T, 588T>C, IVS5-55C>T, IVS7+20G>A, and IVS7-141T>A). No non-synonymous mutation was detected. We genotyped three exonic polymorphisms and performed a case control study and a transmission disequilibrium test using 55 independent complete trios with FS and 106 control subjects. None of these polymorphic alleles were significantly associated with FS. Our results indicate that genomic variations of GABRG2 are not likely to be substantially involved in the etiology of FS in the Japanese population.

No evidence for gamma‐interferon mediated haematopoietic inhibition by T cells in aplastic anaemia: an observation in the course of immunosuppressive therapy

Two patients with aplastic anaemia were treated with immunosuppressive agents and peripheral blood T cells were cryopreserved serially. Inhibitory activity of T cells to autologous CFU‐E, γ‐IFN production by T cells and T cell subpopulations were assayed after remission. Inhibitory activity to autologous CFU‐E was not correlated with the numbers or ratios of T cell subpopulations. γ‐IFN production by T cells were within the normal range when inhibitory activity was found. In addition, γ‐IFN production increased after haematopoietic recovery. These findings suggest that γ‐IFN is not a soluble mediator of T cell‐mediated haematopoietic inhibition in aplastic anaemia.

Failure to find evidence for association between voltage-gated sodium channel gene SCN2A variants and febrile seizures in humans

The voltage-gated sodium channel type II alpha polypeptide gene (SCN2A) R188W mutation with channel dysfunction was recently identified in a patient with febrile and afebrile seizures. A possible association between SCN2A R19K polymorphism and febrile seizures (FS) associated with afebrile seizures including generalized epilepsy with febrile seizures plus (GEFS+) was also noted. We attempted to identify the R188W mutation and confirm association of the R19K polymorphism in 93 Japanese patients with FS, 35 Japanese patients with FS associated with afebrile seizures including GEFS+, and 100 control subjects. The R188W mutation was not found. There were no significant differences in genotype or allele frequencies of the R19K polymorphism between groups. Our study failed to provide evidence supporting a causal relation between the SCN2A mutation/polymorphism and FS or FS associated with afebrile seizures including GEFS+ in the Japanese population.

Intravenous gammaglobulin therapy for thromboneutropenic neonates of mothers with systemic lupus erythematosus

i.v. IgG therapy was used to treat thromboneutropenia in 2 male neonates of mothers with SLE. The mothers of both neonates were thrombocytopenic but not neutropenic during the last 3 months of their pregnancies. Anti‐platelet and anti‐neutrophil IgG directed against platelets and neutrophils from the neonates were detected in the sera of both mothers. The platelet and neutrophil counts increased significantly with i.v. IgG therapy in both neonates, i.v. IgG therapy is a safe and effective regimen for passive immune thromboneutropenia.

The effectiveness of O2 administration for transient ischemic attacks in moyamoya disease in children

Moyamoya disease is a cerebrovascular obstructive disease of unknown etiology. The rebuild-up phenomenon, slowing of waves on electroencephalogram (EEG) seen after cessation of hyperventilation (HV), is one of the characteristic phenomena of the disease and is though to be related to a development of its symptoms. Therefore, we investigated the mechanism involved in the rebuild-up phenomenon to clarify the mechanism of development of transient ischemic attack (TIA) in moyamoya disease. Ten patients with moyamoya disease were studied; they ranged in age from 7 to 17 years. The power spectra of the EEGs in the occipital region were obtained with a Berg Fourier EEG analyzer for quantitative analysis. Arterial blood gas change (pH,PaO2,PaCO2), respiratory pattern (abdominal and nasal), tidal volume and respiratory rate were analyzed simultaneously every 30 s-1 min before, during, and after HV. The slow wave power spectrum (rebuild-up) increased and symptoms of TIA developed as a result of the sharp decrease inPaO2 (PaO2 60.5±15.4 mmHg) after cessation of HV. Based on the fact that hypoxemia was playing a main role, 100% oxygen was administered at a rate of 0.5 l/min in 4 cases where the rebuild-up phenomenon was clear. The EEG power spectra and arterial blood gas were analyzed during rebuild-up with and without O2 administration. The effectiveness of O2 administration at the beginning of rebuild-up as measure to prevent the symptoms was checked by a recovery rate of slow wave power percentage, a recovery time of slow wave power percent and by clinical observation. The recovery rates were 11.8±4.2% min and 5.5±4.0% min with and without O2 inhalation, respectively (P< 0.001). Recovery times of slow wave power percentage were 4.3±1.8 min and 8.1±1.2 min with and without O2 inhalation, respectively (P< 0.01). Thus, oxygen administration soon after the cessation of HV was shown to be effective in eliminating the rebuild-up phenomenon and hence in abolishing its symptoms.

Simultaneous transient erythroblastopenia and agranulocytosis: IgG-mediated inhibition of erythrogranulopoiesis.

We report a case of simultaneous transient erythroblastopenia and agranulocytosis recovering spontaneously. In vitro study using autologous bone marrow cells after recovery demonstrated IgG‐mediated inhibition of both erythropoiesis and gran‐ulopoiesis but not megakaryopoiesis. The inhibitory activity disappeared shortly after remission. These findings suggest that IgG‐mediated inhibition of hematopoiesis may be pathogenetic for transient bone marrow failure of the patient.