Saori Tanabe

Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate‐glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese

We analyzed the bilirubin uridine diphosphate‐glucuronosyltransferase (B‐UGT) gene in 42 Japanese newborns with hyperbilirubinemia and determined that 21 infants were heterozygous while 3 was homozygous for Gly71Arg. Allele frequency of Gly71Arg was 0.32 in newborns with hyperbilirubinemia, which was significantly higher than 0.13 in healthy Japanese controls. This mutant allele is also prevalent among Korean and Chinese healthy controls with a frequency of 0.23 in both populations. However, this mutation was not detected in 50 healthy German controls. These data suggest that the high frequency of the Gly71Arg mutation of the B‐UGT gene is associated with high incidence of neonatal hyperbilirubinemia in Japanese, Korean and Chinese populations.

Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese

AbstractNeonatal hyperbilirubinemia, which is prevalent among Asian peoples, has been considered as a physiological phenomenon, and its metabolic basis has not been clearly explained. Gilbert syndrome is a common inherited disease of unconjugated hyperbilirubinemia due to decreased bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT), and its role in neonatal jaundice has recently been considered. We have previously reported that the Gly71Arg mutation of the B-UGT gene associated with Gilbert syndrome is prevalent in Japanese, Korean, and Chinese populations and was more frequently detected in neonates with severe hyperbilirubinemia than in control subjects. We have studied 159 Japanese full-term neonates, evaluating the relationship between the B-UGT genotype and the severity of jaundice, as assessed with a transcutaneous bilirubinometer. The gene frequency of the Gly71Arg mutation in these neonates was 0.19, and neonates carrying the Gly71Arg mutation had significantly increased bilirubin levels on days 2–4, manifested in a gene dose-dependent manner. The frequency of the Gly71Arg mutation was 0.47 in the neonates who required phototherapy (i.e., those with more severe hyperbilirubinemia), significantly higher than 0.16 in the neonates who did not require the therapy. The gene frequency of the TA repeat promoter polymorphism, the (TA)7 mutation, was 0.07, and neonates carrying this mutation did not have an increase in bilirubin. These results suggested that the Gly71Arg mutation contributes to the high incidence of neonatal hyperbilirubinemia in Japanese.

Targeted capture and sequencing for detection of mutations causing early onset epileptic encephalopathy.

Early onset epileptic encephalopathies (EOEEs) are heterogeneous epileptic disorders caused by various abnormalities in causative genes including point mutations and copy number variations (CNVs). In this study, we performed targeted capture and sequencing of a subset of genes to detect point mutations and CNVs simultaneously.

Clinical correlations of mutations affecting six components of the SWI/SNF complex: Detailed description of 21 patients and a review of the literature

Mutations in the components of the SWItch/sucrose nonfermentable (SWI/SNF)‐like chromatin remodeling complex have recently been reported to cause Coffin–Siris syndrome (CSS), Nicolaides–Baraitser syndrome (NCBRS), and ARID1B‐related intellectual disability (ID) syndrome. We detail here the genotype‐phenotype correlations for 85 previously published and one additional patient with mutations in the SWI/SNF complex: four with SMARCB1 mutations, seven with SMARCA4 mutations, 37 with SMARCA2 mutations, one with an SMARCE1 mutation, three with ARID1A mutations, and 33 with ARID1B mutations. The mutations were associated with syndromic ID and speech impairment (severe/profound in SMARCB1, SMARCE1, and ARID1A mutations; variable in SMARCA4, SMARCA2, and ARID1B mutations), which was frequently accompanied by agenesis or hypoplasia of the corpus callosum. SMARCB1 mutations caused “classical” CSS with typical facial “coarseness” and significant digital/nail hypoplasia. SMARCA4 mutations caused CSS without typical facial coarseness and with significant digital/nail hypoplasia. SMARCA2 mutations caused NCBRS, typically with short stature, sparse hair, a thin vermillion of the upper lip, an everted lower lip and prominent finger joints. A SMARCE1 mutation caused CSS without typical facial coarseness and with significant digital/nail hypoplasia. ARID1A mutations caused the most severe CSS with severe physical complications. ARID1B mutations caused CSS without typical facial coarseness and with mild digital/nail hypoplasia, or caused syndromic ID. Because of the common underlying mechanism and overlapping clinical features, we propose that these conditions be referred to collectively as “SWI/SNF‐related ID syndromes”.

Severe hypertension and cardiac failure associated with neuroblastoma: A case report

The authors report on 3-year-old-girl with neuroblastoma complicated by severe hypertension and cardiac failure. She had cardiomegaly and pleural and pericardial effusions. Echocardiogram showed left ventricular hypertrophy and decrease of the left ventricular ejection fraction to 0.36 (normal > .40). Abdominal computed tomographic scan indicated a 7 x 7-cm tumor in the left suprarenal area. There was a marked increase in catecholamines and metabolites in her body fluids. After hypertension was controlled with doxazosin (a long-acting alpha 1 adrenergic blocker), her cardiac function gradually improved. A tumor was surgically removed and diagnosed as a poorly differentiated ganglioneuroblastoma. Preoperative differentiation between neuroblastoma and pheochromocytoma was not possible on the basis of catecholamine analysis or imaging studies including computed tomography scan and magnetic resonance imaging. It is important to control hypertension quickly in the patients with catecholamine-induced cardiomyopathy to facilitate surgical intervention for diagnosis and treatment.

Terminal deletion of chromosome 10q: clinical features and literature review.

Key words chromosome 10q, deletion.

Association of genomic deletions in the STXBP1 gene with Ohtahara syndrome.

To the Editor : Ohtahara syndrome (OS) is characterized by early-onset of seizures, suppression-burst patterns on electroencephalogram (EEG), and severe psychomotor retardation (1–3). De novo mutations in the STXBP1 gene, including various point mutations and one complete deletion, have been found in about one-third of Japanese cases of cryptogenic OS (4–6). However, the clinical spectrum of STXBP1 mutations can be applied to other pathologies. For instance, in one study, STXBP1 abnormalities including a microdeletion were detected in approximately 10% of patients (5/49) with early-onset epileptic encephalopathy that did not fit into a specific epilepsy syndrome (7). Other studies have also detected de novo STXBP1 mutations in 2 of 95 individuals with mental retardation and non-syndromic epilepsy (8), in addition to the detection of a de novo partial deletion in a child with epilepsy and autistic features (9, 10). On the basis of these findings, extensive genetic testing including copy number analysis of STXBP1 should be considered in children with early-onset seizures. However, the use of high-resolution copy number analysis of STXBP1 thus far has been limited. In this study, we performed customized array comparative genomic hybridization (aCGH) analysis, in which a total of 27,026 probes covering

Beraprost sodium for pulmonary hypertension with congenital heart disease.

Beraprost sodium (BPS) is an oral prostacyclin (PGI2) analog newly developed in Japan.1 Although short-term BPS reduces pulmonary vascular resistance (PVR) in patients with secondary pulmonary hypertension (PH),2,3 there have been few reports of the long-term effect of BPS for those patients.3,4 We report two infants with PH associated with congenital heart disease (CHD) successfully treated with long-term BPS administration.

Two newborn-onset patients of Upshaw-Schulman syndrome with distinct subsequent clinical courses

Upshaw–Schulman syndrome (USS) is caused by a congenital deficit in ADAMTS13 activity owing to genetic mutations. USS is characterized by severe neonatal jaundice with a negative Coombs test and repeated childhood episodes of thrombocytopenia reversible by fresh frozen plasma (FFP) infusions. We present two patients with USS, both of whom underwent exchange blood transfusions as newborns, although the disease subsequently developed along different clinical courses. USS-CC5 initially received a diagnosis of neonatal jaundice due to fetomaternal ABO incompatibility with an indirect positive Coombs test, which masked the diagnosis of USS. Before prophylactic FFP infusions were initiated, USS-CC5 had chronic thrombocytopenia. In contrast, thrombocytopenia developed in USS-HH4 only in response to infections and spontaneously normalized without FFP infusions. Analyses of the ADAMTS13 genes in USS-CC5 and USS-HH4 revealed compound heterozygotes of p.R398C/p.Q723K and p.Q449X/p.Q1374Sfs, respectively. Analysis of von Willebrand factor (VWF) multimers in plasma samples taken from both patients in remission showed single symmetrical multimer bands, which differ from the triplet structure of bands observed in normal samples. These data suggested that plasma VWF multimers in the patients had not been proteolytically modified. Our results indicate the presence of a previously unknown regulatory mechanism for VWF-dependent high-shear stress-induced platelet aggregation.

A new form of total anomalous pulmonary venous connection with double drainage

an uncommon congenital heart disease in which all of the pulmonary veins connect to the right atrium or one of its tributaries. It is conventionally classified by the site of drainage of the pulmonary venous blood flow: supracardiac, cardiac, infracardiac and mixed types.1 Recently, the double connection type of TAPVC in which all pulmonary veins drain to a confluence that drains into two different sites, usually into the coronary sinus and the left innominate vein, has been reported.2–4 We describe a new form of TAPVC with double connection and discuss the embryogenesis of this uncommon anomaly.