Tokyo Metropolitan Kiyose Childrens Hospital

Kiyose, Japan

Tokyo Metropolitan Kiyose Childrens Hospital

Kiyose, Japan
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Cho T.-J.,Seoul National University | Kim O.-H.,Ajou University | Choi I.H.,Seoul National University | Nishimura G.,Tokyo Metropolitan Kiyose Childrens Hospital | And 4 more authors.
Journal of Medical Genetics | Year: 2010

A three-generation family with four patients affected by a novel mesomelic dysplasia was investigated for genome-wide DNA copy number variation profiles. This revealed a microduplication of a 1.0-Mb chromosomal segment at 2q31.1 spanning nine Homeo box D (HOXD) genes that co-segregated with the phenotype. Quantitative PCR analysis of a gene within this duplicated region showed consistent results. Mesomelic dysplasia Kantaputra type (MDK; MIM 156232),which shares some phenotypes with this family, has also been mapped to a chromosomal region comprising 2q31.1, raising the possibility that MDK and the condition observed in this family may be allelic.

Unger S.,University of Lausanne | Gorna M.W.,Austrian Academy of Sciences | Le Bechec A.,Swiss Institute of Bioinformatics | Do Vale-Pereira S.,University of Lausanne | And 20 more authors.
American Journal of Human Genetics | Year: 2013

Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth. © 2013 The American Society of Human Genetics.

Shishido S.,Toho University | Hyodo Y.Y.,Toho University | Aoki Y.,Toho University | Takasu J.,Toho University | And 6 more authors.
Transplantation Proceedings | Year: 2012

Background: Due to the profound shortage of suitable deceased allografts, much effort has been made to investigate whether successful kidney transplantation (KT) is possible across the ABO blood group barrier even for pediatric recipients. Methods: We reviewed 52 consecutive ABO incompatible (ABOic) transplantation performed between September 1989 and March 2011. The mean age at transplantation was 10.6 ± 3.9 years (range, 4.419.7), with 35 boys and 17 girls. The donor-to-recipient ABO blood antigen incompatibility was as follows: A1/O (n = 17); B/O (n = 13); A1/B (n = 6); B/A1 (n = 1); A1B/B (n = 9); and A1B/A (n = 6). As a control group, data were collected from 271 pediatric ABO compatible (ABOc) living donor KT in the same period. Results: Overall acute rejection episodes (ARE) among the ABOic group were significantly higher than those of the ABOc group (44% vs 26%; P <.02). However, there was no difference in glomerular filtration rate (GFR) at 1 year after transplantation: 86 ± 31 mL/min for ABOic vs 99 ± 37 mL/min for ABOic, respectively. The 1-y, 5-y, and 10-year patient survival rates were 98%, 92%, and 92% in the ABOic group, respectively, and 99%, 98%, and 97% in the ABOc group, respectively (P = not significant [NS]). The overall 1-, 5-, 10-, and 15-year graft survival rates were 94%, 88%, 86%, and 86% in the ABOic group, respectively, and 95%, 92%, 88%, and 78% in the ABOc group, respectively. Conclusion: ABOic KT provided long-term allograft and patient survivals equivalent to ABOc live donor transplantations. © 2012 Published by Elsevier Inc.

Shishido S.,Toho University | Satou H.,Tokyo Metropolitan Kiyose Childrens Hospital | Muramatsu M.,Toho University | Hamasaki Y.,Toho University | And 5 more authors.
Clinical Transplantation | Year: 2013

Background: Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric kidney allografts is associated with poor graft survival. Several therapeutic regimens have been proposed, with conflicting results. Methods: Ten pediatric patients with recurrent FSGS after kidney transplantation were treated with a protocol of methylprednisolone (MP) infusions in combination with cyclosporine (CsA)-based immunosuppression. The patients received a drug regimen with infusions of 20 mg/kg MP on three consecutive days at week 1, week 3, and week 5, and then monthly until six months after transplantation. If a complete or partial remission (PR) was obtained, MP pulse continued every three months until 24 months after transplantation. The CsA dose was adjusted according to AUC0-4. Results: Seven of 10 patients (70%) achieved complete remission (CR) with stable renal function within 18 months of beginning of treatment. One of two patients with PR entered CR 3.5 yr after transplantation. One patient lost her graft due to recurrence four months after transplantation. After observation for 26-119 months, seven patients maintained remission with normal glomerular filtration rate. Few major side effects were observed in association with the high-dose MP infusion therapy. Conclusions: MP infusion therapy in combination with CsA-based immunosuppression could be safe and effective in treating recurrent FSGS after kidney transplantation. © 2013 John Wiley & Sons A/S.

Goto M.,Tokyo Metropolitan Hachioji Childrens Hospital | Mabe H.,Kumamoto University | Nishimura G.,Tokyo Metropolitan Kiyose Childrens Hospital | Katsumata N.,National Health Research Institute
Journal of Pediatric Endocrinology and Metabolism | Year: 2010

Progressive osseous heteroplasia (POH), characterized by progressive heterotopic ossifications of the dermis, skeletal muscle and deep connective tissues, is caused by inactivating mutations of GNAS1 of a paternally transmitted allele. We report a novel GNAS1 mutation in a patient with POH. The patient is a 6 year-old boy, whose short stature came to medical attention in infancy. He was diagnosed with growth hormone (GH) deficiency, and subsequent GH therapy resulted in catch-up growth. He developed soft tissue masses in the right heel and right elbow that were calcified or ossified on plain radiographs. MR imaging raised a suspicion of heterotopic ossification; thus, GNAS1 was analyzed. A novel nonsense mutation p.R342X was observed in the patient, but not in his parents. Single nucleotide polymorphism analysis revealed paternal transmission of the mutant allele. RT-PCR analysis demonstrated expression of both normal and mutant GNAS1 transcripts in the patient. Thus, the patient is considered to have developed POH because of the non-functioning truncated G sα protein. © Freund Publishing House Ltd.

Miyake N.,Yokohama City University | Kosho T.,Shinshu University | Mizumoto S.,Hokkaido University | Furuichi T.,RIKEN | And 21 more authors.
Human Mutation | Year: 2010

Ehlers-Danlos syndrome (EDS) is a heterogeneous connective tissue disorder involving skin and joint laxity and tissue fragility. A new type of EDS, similar to kyphoscoliosis type but without lysyl hydroxylase deficiency, has been investigated. We have identified a homozygous CHST14 (carbohydrate sulfotransferase 14) mutation in the two familial cases and compound heterozygous mutations in four sporadic cases. CHST14 encodes dermatan 4-O-sulfotransferase 1 (D4ST1), which transfers active sulfate from 3′-phosphoadenosine 5′-phosphosulfate to position 4 of the N-acetyl-Dgalactosamine (GalNAc) residues of dermatan sulfate (DS). Transfection experiments of mutants and enzyme assays using fibroblast lysates of patients showed the loss of D4ST1 activity. CHST14 mutations altered the glycosaminoglycan (GAG) components in patients' fibroblasts. Interestingly, DS of decorin proteoglycan, a key regulator of collagen fibril assembly, was completely lost and replaced by chondroitin sulfate (CS) in the patients' fibroblasts, leading to decreased flexibility of GAG chains. The loss of the decorin DS proteoglycan due to CHST14 mutations may preclude proper collagen bundle formation or maintenance of collagen bundles while the sizes and shapes of collagen fibrils are unchanged as observed in the patients' dermal tissues. These findings indicate the important role of decorin DS in the extracellular matrix and a novel pathomechanism in EDS. © 2010 Wiley-Liss, Inc.

Fukuzawa R.,University of Otago | Fukuzawa R.,Tokyo Metropolitan Kiyose Childrens Hospital | Holman S.K.,University of Otago | Chow C.W.,Royal Melbourne Hospital | And 5 more authors.
Journal of Medical Genetics | Year: 2010

Background: Somatic mutations in the X-linked tumour suppressor gene WTX have been observed in 6- 30% of sporadic cases of Wilms tumour. Germline mutations in the same gene cause the sclerosing skeletal dysplasia, osteopathia striata congenita with cranial sclerosis (OSCS). No evidence points towards a susceptibility to the development of tumours in individuals with OSCS, suggesting that there are unrecognised additional determinants that influence the phenotypic outcome associated with germline mutations in WTX. One explanation may be that a somatic mutation in WTX may need to occur late in tumour development to contribute to tumourigenesis. Methods: Here a panel of four sporadic Wilms tumours with associated nephrogenic rest tissue and characterised WTX and CTNNB1 mutations is studied to ascertain the temporal sequence of acquisition of these mutations. Additionally, a family with OSCS is described segregating a germline mutation in WTX and manifesting a lethal phenotype in males. One male from this family had bilateral multifocal nephrogenic rests at autopsy. Results: In one of the four tumours the WTX mutation was present in both tumour and rest tissue indicating it had arisen early in tumour development. In the remaining three tumours, the WTX mutation was present in the tumour only indicating late acquisition of these mutations. Conclusions: These data indicate that WTX mutations can arise both early and late in Wilms tumour development. WTX mutations may predispose to nephrogenic rest development rather than Wilms tumour per se.

Ichino M.,Health Science University | Kusaka M.,Health Science University | Kuroyanagi Y.,Health Science University | Mori T.,Health Science University | And 6 more authors.
Journal of Urology | Year: 2010

Purpose: Renal scarring is a serious complication that often occurs with chronic pyelonephritis in the presence of vesicoureteral reflux. In a previous study we established a rat model of renal scarring in which we found the up-regulation of neutrophil-gelatinase associated lipocalin at the mRNA and protein levels. In this study we evaluated urinary neutrophil-gelatinase associated lipocalin as a potential biomarker for progression of renal scarring in patients with vesicoureteral reflux. Materials and Methods: A total of 34 patients diagnosed with vesicoureteral reflux without evidence of current urinary tract infection and 28 normal healthy children were enrolled in this study. Renal scars were evaluated by 99mtechnetium dimercapto-succinic acid renal scan in 24 of the reflux cases. Urinary neutrophil-gelatinase associated lipocalin levels were monitored by ELISA. Results: In normal subjects urinary neutrophil-gelatinase associated lipocalin was high during infancy, decreased rapidly within the following year and reached a low stable level from age 3 years onward. Urinary neutrophil-gelatinase associated lipocalin levels, normalized to age matched standards, were significantly increased in patients with vesicoureteral reflux compared to controls. These levels did not correlate with reflux grade, but were significantly higher in patients with radiological evidence of renal scarring irrespective of reflux grade. Conclusions: Estimation of urinary neutrophil-gelatinase associated lipocalin may be useful as a noninvasive diagnostic or prognostic biomarker for renal scarring. © 2010 American Urological Association Education and Research, Inc.

Miyauchi J.,Tokyo Dental College | Ito Y.,National Center for Child Health and Development | Tsukamoto K.,National Center for Child Health and Development | Takahashi H.,Tokyo Metropolitan Otsuka Hospital | And 3 more authors.
British Journal of Haematology | Year: 2010

Mutations of GATA1, leading to aberrant expression of a truncated form of GATA1 (called GATA1s), are present in transient leukaemia (TL) in neonates with Down syndrome. Using these molecular markers of TL, we investigated the growth and differentiation potential of TL blasts in the presence of hematopoietic growth factors (HGFs). Interleukin-3, stem cell factor and granulocyte- macrophage colony-stimulating factor potently stimulated the growth of TL blast progenitors and induced differentiation towards basophil/mast cell lineages, whereas thrombopoietin induced differentiation towards megakaryocytes. GATA1s was expressed in TL blasts in all five patients examined but was down-regulated during differentiation induced by these HGFs, while full-length GATA1 was not expressed throughout the culture. GATA1 mutations were detected in TL blasts in four patients, including one patient with two distinct mutations. The cells of this patient exhibited identical and only mutated sequences both before and after culture with HGFs, confirming the leukemic cell origin of these differentiated cells. Erythroid differentiation of TL blasts was not evident with any HGFs. These data indicate that TL blasts have the potential to grow and differentiate towards particular hematopoietic lineages in the presence of specific HGFs and that the down-regulation of GATA1s might be involved in blast cell differentiation. © 2010 Blackwell Publishing Ltd.

PubMed | Tokyo Metropolitan Kiyose Childrens Hospital
Type: Case Reports | Journal: No to hattatsu. Brain and development | Year: 2013

A 8-year-old girl was hospitalized with consciousness disturbance and involuntary movements five days after the onset of fever. Cranial MRI revealed symmetrical involvement of the bilateral basal ganglia with elevated ADC mapping, suggesting vasogenic edema.Her clinical symptoms improved with methylprednisolone pulse therapy without neurological sequelae. The rapid antigen test for group A beta-hemolytic streptococcus was positive and serum ASO was elevated. Myelin basic protein in cerebrospinal fluid was elevated. We suggest that the pathophysiological mechanism in the present case was not necrotic/cytotoxic but autoimmune inflammation, which is compatible with acute disseminated encephalomyelitis associated with streptococcal infection.

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