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Biomedical subjects

Junko Kanno

Publications and source records attributed to Junko Kanno.

7 recordsLinked to original sources
PubMed2025

DHX37 variants in patients with 46,XY disorders or differences of sex development.

Here, using whole-exome sequencing of a cohort of 17 Japanese patients with 46,XY disorders or differences of sex development, we identified two pathogenic DEAH-box helicase 37 (DHX37) variants in three patients. We also identified a patient with a likely pathogenic variant in SOX9 and a rare likely benign variant in DHX37. This Data Report highlights the genetic and phenotypic diversity of DXH37 variants.

Journal Article↗
PubMed2006

A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.

Autosomal-dominant, nonsyndromic hearing impairment is clinically and genetically heterogeneous. We encountered a large Japanese pedigree in which nonsyndromic hearing loss was inherited in an autosomal-dominant fashion. A genome-wide linkage study indicated linkage to the DFNA2 locus on chromosome 1p34. Mutational analysis of KCNQ4 encoding a potassium channel revealed a novel one-base deletion in exon 1, c.211delC, which generated a profoundly truncated protein without transmembrane domains (p.Q71fsX138). Previously, six missense mutations and one 13-base deletion, c.211_223del, had been reported in KCNQ4. Patients with the KCNQ4 missense mutations had younger-onset and more profound hearing loss than patients with the 211_223del mutation. In our current study, 12 individuals with the c.211delC mutation manifested late-onset and pure high-frequency hearing loss. Our results support the genotype-phenotype correlation that the KCNQ4 deletions are associated with later-onset and milder hearing impairment than the missense mutations. The phenotypic difference may be caused by the difference in pathogenic mechanisms: haploinsufficiency in deletions and dominant-negative effect in missense mutations.

Asian People↗
PubMed2006

De novo and salvage pathways of DNA synthesis in primary cultured neurall stem cells.

We studied the de novo and salvage pathways of DNA synthesis in sphere-forming neural stem cells obtained from mouse embryos by a neurosphere method. The former pathway needs folic acid (FA) for nucleotide biosynthesis, while the latter requires deoxyribonucleosides (dNS). We examined the proliferative activity of sphere-forming cells in E14.5 embryos by counting the number of spheres formed in media that lacked FA and/or dNS. Proliferation failure and apoptosis occurred in a deficient medium lacking of both FA and dNS. Spheres formed in the deficient medium supplemented with dNS, without FA, did not produce neuron, but rather only seem to generate astrocytes and oligodendrocytes when plated under differentiation condition in culture. On the other hand, a subpopulation of cultured cells formed spheres in the deficient medium supplemented with FA alone in an appropriate concentration, and did possess the self-renewing and multipotential characteristics of neural stem cells. Spheres formed in the media containing low dose Azathioprine and methotrexate, inhibitors of de novo DNA synthesis, were selectively prevented from producing neurons even in the presence of FA. These results suggested that activating de novo DNA synthesis was needed for neural stem cells to proliferate with multipotentiality.

Age Factors↗
PubMed2006

Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation.

OBJECTIVE: To determine whether the devastating outcome of neonatal-onset glycine encephalopathy (NKH) could be improved by instituting treatment immediately at birth rather than after symptoms are already well established. METHODS: A newborn with NKH diagnosed prenatally following the neonatal death of a previous affected sibling was treated from birth with oral sodium benzoate (250 mg/kg/day) and the NMDA receptor antagonist ketamine (15 mg/kg/day) immediately after sampling cord blood and cerebrospinal fluid (CSF) for glycine determination. Glycine cleavage system (CGS) activity was determined in placental tissue. Mutation analysis was performed by sequencing all GLDC, GCSH and AMT exons. RESULTS: CSF glycine (99 micromol/L, reference 3.8-8.0) was already markedly elevated at birth. GCS activity in placental tissue was severely reduced (2.6% of controls). A novel homozygous GLDC c.482A-->G(Y161C) missense mutation was identified. Neonatal hypotonia and apnea did not occur but the long-term outcome was poor, with intractable seizures and severe psychomotor retardation. This contrasts with the favorable outcome with early treatment in variant NKH with mild GCS deficiency (Ann Neuol 2004;56:139-143). INTERPRETATION: Prospective treatment with this regimen can favorably modify the early neonatal course of severe NKH but does not prevent the poor long-term outcome, suggesting glycine-induced prenatal injury and/or ongoing postnatal damage.

Aldehydes↗
PubMed2006

Rapid diagnosis of glycine encephalopathy by 13C-glycine breath test.

OBJECTIVE: It is currently problematic to confirm the clinical diagnosis of glycine encephalopathy, requiring either invasive liver biopsy for enzymatic analysis of the glycine cleavage system or exhaustive mutation analysis. Because the glycine cleavage system breaks down glycine generating carbon dioxide, we suppose that the glycine cleavage system activity could be evaluated in vivo by measuring exhaled (13)CO(2) after administration of [1-(13)C]glycine. METHODS: The [1-(13)C]glycine breath test was performed in 10 control subjects and 5 glycine encephalopathy patients with GLDC mutation, including 1 patient with mild glycine encephalopathy. RESULTS: All the patients showed lower (13)CO(2) excretion than any control subject. INTERPRETATION: Not only typical GE but also atypical GE can be reliably diagnosed by the (13)C-glycine breath test. Because it is rapid, non-invasive, and requires little expertise, the breath test could be useful as a standard test for diagnosing GE.

Adolescent↗
PubMed2005

A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem.

Glycine encephalopathy (GE) (non-ketotic hyperglycinemia) is an autosomal recessive neurometabolic disease caused by defective activity of the glycine cleavage system. Clinically, patients present usually in the neonatal period with hypotonia, encephalopathy, hiccups and breath arrests with or without overt seizures. GE is considered rare, but its incidence is relatively high in several geographical areas around the world. We report a novel mutation causing GE in six extended Arab families, all from a small suburban village (population 5,000). A methionine to threonine change in the initiation codon of the glycine decarboxylase gene led to markedly reduced glycine decarboxylase mRNA levels and abolished glycine cleavage system activity.

Amino Acid Oxidoreductases↗