Language：English   Publisher：Scientific Reports  

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24–35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

DOI： 10.1038/s41598-022-14161-6

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Language：English   Publisher：Brain and Development  

Background: MICPCH is manifested as microcephaly associated with pontocerebellar hypoplasia and global developmental delay but developmental regression has never been reported. We describe the detailed clinical history of a woman with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH) with a CASK mutation who exhibited gross motor regression after adolescence. Case: The patient experienced severe motor and intellectual developmental delay with microcephaly from infancy. The initial diagnosis was Rett syndrome based on her clinical features, including hand stereotypes and the absence of structural abnormality on magnetic resonance imaging (MRI) performed at the age of 5 years. Although gross motor abilities developed slowly and she could walk independently, she never acquired speech or understanding of languages. After adolescence, her motor ability gradually regressed so that she was unable to stand without support and moved with a wheelchair. At the age of 31 years, because of her atypical clinical course for Rett syndrome, whole exome sequencing was performed, which revealed a de novo heterozygous c.2068 + 1G > A mutation in the CASK gene (NM_001126055). Brain MRI revealed mild pontocerebellar hypoplasia compatible with the clinical phenotype of MICPCH. Discussion: This case suggests that MICPCH with a CASK mutation might cause developmental regression after adolescence and might be regarded as a neurodegenerative disorder.

DOI： 10.1016/j.braindev.2020.11.007

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Language：English   Publisher：Journal of Infection and Chemotherapy  

Cytomegalovirus (CMV) is one of the major infectious etiologies that induce thrombocytopenia. Although immune thrombocytopenic purpura (ITP) in children is often preceded by viral infections, thrombocytopenia associated with active CMV infection is considered CMV-related thrombocytopenia (CMV-thrombocytopenia), which can be distinguished from ITP. CMV-thrombocytopenia is reported to be less responsive to standard therapies for ITP and may require antiviral therapies. We herein report a case of refractory CMV-thrombocytopenia that achieved complete remission without antiviral therapy. A 20-month-old boy presented with a 2-day history of fever and systemic petechiae. There were no abnormal findings except for an extremely low platelet count (8000/μl) on blood examinations. He was clinically diagnosed with ITP, and intravenous immunoglobulin was administered twice, but his platelet count did not increase. CMV infection was suspected serologically, and a high CMV DNA load was detected in serum by real-time quantitative polymerase chain reaction (PCR). Without antiviral treatment, the CMV DNA load decreased below the detection limit on the 11th day of admission, followed by complete remission of the thrombocytopenia. The present case suggests that spontaneous recovery of thrombocytopenia can be expected in immunocompetent patients with CMV-thrombocytopenia in whom decreased CMV DNA load is observed.

DOI： 10.1016/j.jiac.2018.06.004

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Language：Japanese   Publisher：JAPAN SOCIETY OF GYNECOLOGIC AND OBSTETRIC ENDOSCOPY AND MINIMALLY INVASIVE THERAPY  

A gastrointestinal stromal tumor (GIST) is the most common type of mesenchymal tumor of the gastrointestinal tract. A GIST often presents with an extra-intestinal growth pattern or peritoneal dissemination. It requires a differential diagnosis that includes malignant gynecologic tumors; however, ovarian metastasis of a GIST is extremely rare. We are reporting a case of a GIST metastatic to the ovary, diagnosed with laparoscopic surgery, which required differentiating from a malignant ovarian tumor. The patient was a 59-year-old woman referred to our department for a detailed evaluation of a left ovarian mass. She had a history of an intestinal GIST at the age of 56, which was completely excised. Three years after the operation, a chest-abdominal computed tomography imaged a left ovarian mass and multiple nodules in the mesentery, greater omentum, and the right lung. Because a GIST seldom metastasizes to the ovary, a diagnostic laparoscopy to differentiate from primary malignant ovarian tumors was performed. A left salpingo-oophorectomy and a biopsy of a peritoneal tumor was performed; the histopathologic diagnosis was a GIST metastatic to the left ovary with peritoneal dissemination. Consequently, the patient underwent molecular targeted therapy. The possibility of a mesenchymal tumor of the gastrointestinal tract such as a GIST should be considered in the differential diagnosis of a pelvic mass. Less invasive laparoscopic surgery facilitates intraperitoneal excision of the tumor and a histological diagnosis. Laparoscopic surgery can be useful for making a definitive diagnosis and treating malignant tumors.

DOI： 10.5180/jsgoe.30.181

CiNii Research

Language：Japanese   Publisher：JAPAN SOCIETY OF GYNECOLOGIC AND OBSTETRIC ENDOSCOPY AND MINIMALLY INVASIVE THERAPY  

A 25-year-old female patient was referred to our hospital because of abdominal pain and an intrapelvic cystic tumor. The cystic lesion was located just under the abdominal wall and the tumor appeared to arise from the left ovary. The patient underwent laparoscopic surgery, which revealed that the tumor was a retroperitoneal cyst. Because the cyst wall was extremely thin, complete excision of the tumor was difficult; thus, laparoscopic fenestration was alternatively performed. A total of 150 mL clear yellow serous fluid was drained; cytology was negative for malignancy. Postoperatively, she conceived and delivered an infant. No recurrence of the tumor was observed. Most retroperitoneal tumors are generally solid and rarely present as a cystic lesion. Complete excision of the tumor is recommended due to the possibility of malignancy. Fenestration of the cyst is also an accepted choice of treatment for cases in which complete excision is difficult and diagnostic imaging studies show no signs of malignancy. Even though retroperitoneal cysts can be safely excised laparoscopically, laparoscopic surgery does not remain a standard treatment for retroperitoneal cysts. Here, we report a case of the retroperitoneal cyst presenting as an intrapelvic cystic tumor. Gynecologists also unexpectedly encounter retroperitoneal cysts because it is difficult to differentiate retroperitoneal cysts from ovarian cysts in some cases. Gynecologists must consider retroperitoneal cysts as a differential diagnosis of intrapelvic cystic tumors and be cognizant of the therapeutic strategies for retroperitoneal cysts.

DOI： 10.5180/jsgoe.30.275

CiNii Research

Language：English   Publisher：Biochemical and Biophysical Research Communications  

O-linked-β-. N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-. N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution. © 2012 Elsevier Inc.

DOI： 10.1016/j.bbrc.2012.01.098

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