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Dive into the research topics where Tomohiro Kohmoto is active.

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Featured researches published by Tomohiro Kohmoto.


Human genome variation | 2014

A novel PTCH1 mutation in a patient with Gorlin syndrome

Nana Okamoto; Takuya Naruto; Tomohiro Kohmoto; Takahide Komori; Issei Imoto

Gorlin syndrome is an autosomal dominant disorder characterized by a wide range of developmental abnormalities and a predisposition to various tumors, and it is linked to the alteration of several causative genes, including PTCH1. We performed targeted resequencing using a next-generation sequencer to analyze genes associated with known clinical phenotypes in an 11-year-old male with sporadic jaw keratocysts. A novel duplication mutation (c.426dup) in PTCH1, resulting in a truncated protein, was identified.


Scientific Reports | 2015

Deep intronic GPR143 mutation in a Japanese family with ocular albinism

Takuya Naruto; Nobuhiko Okamoto; Kiyoshi Masuda; Takao Endo; Yoshikazu Hatsukawa; Tomohiro Kohmoto; Issei Imoto

Deep intronic mutations are often ignored as possible causes of human disease. Using whole-exome sequencing, we analysed genomic DNAs of a Japanese family with two male siblings affected by ocular albinism and congenital nystagmus. Although mutations or copy number alterations of coding regions were not identified in candidate genes, the novel intronic mutation c.659-131 T > G within GPR143 intron 5 was identified as hemizygous in affected siblings and as heterozygous in the unaffected mother. This mutation was predicted to create a cryptic splice donor site within intron 5 and activate a cryptic acceptor site at 41nt upstream, causing the insertion into the coding sequence of an out-of-frame 41-bp pseudoexon with a premature stop codon in the aberrant transcript, which was confirmed by minigene experiments. This result expands the mutational spectrum of GPR143 and suggests the utility of next-generation sequencing integrated with in silico and experimental analyses for improving the molecular diagnosis of this disease.


Human genome variation | 2016

A novel missense mutation of COL5A2 in a patient with Ehlers-Danlos syndrome.

Miki Watanabe; Ryuji Nakagawa; Takuya Naruto; Tomohiro Kohmoto; Kenichi Suga; Aya Goji; Shoji Kagami; Kiyoshi Masuda; Issei Imoto

Ehlers–Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. For molecular diagnosis, targeted exome sequencing was performed on a 9-year-old male patient who was clinically suspected to have EDS. The patient presented with progressive kyphoscoliosis, joint hypermobility and hyperextensible skin without scars. Ultimately, classical EDS was diagnosed by identifying a novel, mono-allelic mutation in COL5A2 [NM_000393.3(COL5A2_v001):c.682G>A, p.Gly228Arg].


Oncotarget | 2017

Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma

Koichiro Kajiura; Kiyoshi Masuda; Takuya Naruto; Tomohiro Kohmoto; Miki Watabnabe; Mitsuhiro Tsuboi; Hiromitsu Takizawa; Kazuya Kondo; Akira Tangoku; Issei Imoto

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.


Human genome variation | 2017

Novel CLCN7 compound heterozygous mutations in intermediate autosomal recessive osteopetrosis

Nana Okamoto; Tomohiro Kohmoto; Takuya Naruto; Kiyoshi Masuda; Takahide Komori; Issei Imoto

Osteopetrosis is a heritable disorder of the skeleton that is characterized by increased bone density on radiographs caused by defects in osteoclast formation and function. Mutations in >10 genes are identified as causative for this clinically and genetically heterogeneous disease in humans. We report two novel missense variations in a compound heterozygous state in the CLCN7 gene, detected through targeted exome sequencing, in a 15-year-old Japanese female with intermediate autosomal recessive osteopetrosis.


Human genome variation | 2016

A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome

Tomohiro Kohmoto; Miki Shono; Takuya Naruto; Miki Watanabe; Kenichi Suga; Ryuji Nakagawa; Shoji Kagami; Kiyoshi Masuda; Issei Imoto

CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)].


Human genome variation | 2015

A novel COL11A1 mutation affecting splicing in a patient with Stickler syndrome.

Tomohiro Kohmoto; Takuya Naruto; Haruka Kobayashi; Miki Watanabe; Nana Okamoto; Kiyoshi Masuda; Issei Imoto; Nobuhiko Okamoto

Stickler syndrome is a clinically and genetically heterogeneous collagenopathy characterized by ocular, auditory, skeletal and orofacial abnormalities, commonly occurring as an autosomal dominant trait. We conducted target resequencing to analyze candidate genes associated with known clinical phenotypes from a 4-year-old girl with Stickler syndrome. We detected a novel heterozygous intronic mutation (NM_001854.3:c.3168+5G>A) in COL11A1 that may impair splicing, which was suggested by in silico prediction and a minigene assay.


Oncotarget | 2016

Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma.

Jun-ichi Hamada; Katsutoshi Shoda; Kiyoshi Masuda; Yuji Fujita; Takuya Naruto; Tomohiro Kohmoto; Yuko Miyakami; Miki Watanabe; Yasusei Kudo; Hitoshi Fujiwara; Daisuke Ichikawa; Eigo Otsuji; Issei Imoto

T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC.


American Journal of Medical Genetics Part A | 2018

A rare male patient with classic Rett syndrome caused by MeCP2_e1 mutation

Narumi Tokaji; Hiromichi Ito; Tomohiro Kohmoto; Takuya Naruto; Rizu Takahashi; Aya Goji; Tatsuo Mori; Yoshihiro Toda; Masako Saito; Shoichiro Tange; Kiyoshi Masuda; Shoji Kagami; Issei Imoto

Rett syndrome (RTT) is a severe neurodevelopmental disorder typically affecting females. It is mainly caused by loss‐of‐function mutations that affect the coding sequence of exon 3 or 4 of methyl‐CpG‐binding protein 2 (MECP2). Severe neonatal encephalopathy resulting in death before the age of 2 years is the most common phenotype observed in males affected by a pathogenic MECP2 variant. Mutations in MECP2 exon 1 affecting the MeCP2_e1 isoform are relatively rare causes of RTT in females, and only one case of a male patient with MECP2‐related severe neonatal encephalopathy caused by a mutation in MECP2 exon 1 has been reported. This is the first reported case of a male with classic RTT caused by a 5‐bp duplication in the open‐reading frame of MECP2 exon 1 (NM_001110792.1:c.23_27dup) that introduced a premature stop codon [p.(Ser10Argfs*36)] in the MeCP2_e1 isoform, which has been reported in one female patient with classic RTT. Therefore, both males and females displaying at least some type of MeCP2_e1 mutation may exhibit the classic RTT phenotype.


American Journal of Medical Genetics Part A | 2017

A 590 kb deletion caused by non‐allelic homologous recombination between two LINE‐1 elements in a patient with mesomelia‐synostosis syndrome

Tomohiro Kohmoto; Takuya Naruto; Miki Watanabe; Yuji Fujita; Sae Ujiro; Nana Okamoto; Hideaki Horikawa; Kiyoshi Masuda; Issei Imoto

Mesomelia‐synostoses syndrome (MSS) is a rare, autosomal‐dominant, syndromal osteochondrodysplasia characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations due to a non‐recurrent deletion at 8q13 that always encompasses two coding‐genes, SULF1 and SLCO5A1. To date, five unrelated patients have been reported worldwide, and MMS was previously proposed to not be a genomic disorder associated with deletions recurring from non‐allelic homologous recombination (NAHR) in at least two analyzed cases. We conducted targeted gene panel sequencing and subsequent array‐based copy number analysis in an 11‐year‐old undiagnosed Japanese female patient with multiple congenital anomalies that included mesomelic limb shortening and detected a novel 590 Kb deletion at 8q13 encompassing the same gene set as reported previously, resulting in the diagnosis of MSS. Breakpoint sequences of the deleted region in our case demonstrated the first LINE‐1s (L1s)‐mediated unequal NAHR event utilizing two distant L1 elements as homology substrates in this disease, which may represent a novel causative mechanism of the 8q13 deletion, expanding the range of mechanisms involved in the chromosomal rearrangements responsible for MSS.

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Issei Imoto

University of Tokushima

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Miki Watanabe

Cincinnati Children's Hospital Medical Center

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Masako Saito

University of Tokushima

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Shoji Kagami

University of Tokushima

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Nobuhiko Okamoto

Boston Children's Hospital

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Aya Goji

University of Tokushima

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Daisuke Ichikawa

Kyoto Prefectural University of Medicine

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