A case of congenital hyperinsulinism presenting with diabetes after long-term diazoxide therapy
AbstractCongenital hyperinsulinism (CHI) is the most common form of persistent hypoglycemia in infants, and diazoxide is the most widely used drug for its treatment. Diazoxide suppresses insulin secretion and attenuates hypoglycemia by binding to sulfonylurea receptor 1 and activating KATP channels. While the short-term side effects of this drug, such as edema and blood cell abnormalities, are well known, the clinical course after its long-term oral administration remains unclear. Furthermore, there are currently no case reports clearly demonstrating a causal relationship between diazoxide and impaired glucose tolerance. W...
Source: Diabetology International - April 16, 2024 Category: Endocrinology Source Type: research
GSE262539 Growth retardation in a mouse model of Kabuki syndrome 2 bears mechanistic similarities to Kabuki syndrome 1.
Contributors : Christine W Gao ; Kasper D Hansen ; Jill A FahrnerSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusGrowth deficiency is a characteristic feature of both Kabuki syndrome 1 (KS1) and Kabuki syndrome 2 (KS2), Mendelian disorders of the epigenetic machinery with similar phenotypes but distinct genetic etiologies. We previously described skeletal growth deficiency in a mouse model of KS1 and further established that a Kmt2d -/- chondrocyte model of KS1 exhibits precocious differentiation. Here we characterized growth deficiency in a mouse model of KS2, Kdm6a tm1d/+. We show t...
Source: GEO: Gene Expression Omnibus - March 30, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism
European Journal of Human Genetics, Published online: 25 March 2024; doi:10.1038/s41431-024-01597-9DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism (Source: European Journal of Human Genetics)
Source: European Journal of Human Genetics - March 25, 2024 Category: Genetics & Stem Cells Authors: Marcello Niceta Andrea Ciolfi Marco Ferilli Lucia Pedace Camilla Cappelletti Claudia Nardini Mathis Hildonen Luigi Chiriatti Evelina Miele Maria Lisa Dentici Maria Gnazzo Claudia Cesario Elisa Pisaneschi Anwar Baban Antonio Novelli Silvia Maitz Angelo Sel Source Type: research
Sex-specific difference in phenotype of Kabuki syndrome type 2 patients: a matched case-control study
Kabuki syndrome (KS) is a monogenic disorder leading to special facial features, mental retardation, and multiple system malformations. Lysine demethylase 6A, (KDM6A, MIM*300128) is the pathogenic gene of Kabuki ... (Source: BMC Pediatrics)
Source: BMC Pediatrics - February 19, 2024 Category: Pediatrics Authors: Yirou Wang, Yufei Xu, Yao Chen, Yabin Hu, Qun Li, Shijian Liu, Jian Wang and Xiumin Wang Tags: Research Source Type: research
Systemic and oral abnormalities in Kabuki syndrome: a case series
This study analyzed the systemic and oral abnormalities in individuals with Kabuki syndrome (KS) that might be investigated to enhance the early diagnosis and treatment by a multidisciplinary team, minimizing the consequences to the individual's health. (Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics)
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - December 29, 2023 Category: ENT & OMF Authors: Lidiane Castro Pinto, Nancy Mizue Kokitsu-Nakata, Gisele da Silva Dalben, Lucas Jos é de Azevedo Silva, Ana Lúcia Pompéia Fraga de Almeida Source Type: research
Systemic and oral abnormalities in Kabuki syndrome – case series
This study analyzed the systemic and oral abnormalities in individuals with Kabuki syndrome (KS) that might be investigated to enhance the early diagnosis and treatment by a multidisciplinary team, minimizing the consequences to the individual's health. (Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics)
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - December 29, 2023 Category: ENT & OMF Authors: Lidiane Castro Pinto, Nancy Mizue Kokitsu-Nakata, Gisele da Silva Dalben, Lucas Jos é de Azevedo Silva, Ana Lúcia Pompéia Fraga de Almeida Source Type: research
Genes, Vol. 15, Pages 48: KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans
Hans T. Bjornsson
Individuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspects of hearing loss, we collected information on hearing status from 21 individuals with KS1 and found that individuals have both sensorineural and conductive hearing loss, with the average age of presentation being 7 years. Our data suggest that while ear infections and structural abnormalities contribute ...
Source: Genes - December 28, 2023 Category: Genetics & Stem Cells Authors: Allison J. Kalinousky Teresa R. Luperchio Katrina M. Schrode Jacqueline R. Harris Li Zhang Valerie B. DeLeon Jill A. Fahrner Amanda M. Lauer Hans T. Bjornsson Tags: Article Source Type: research
GSE246058 Somatic mutations of MLL4/COMPASS induce cytoplasmic localization providing insight into cancer prognosis and treatment
We report that the mutations which cause MLL4 protein truncation also alter its subcellular localization, resulting in loss-of-function in the nucleus and gain-of-function in the cytoplasm. We demonstrate that isogenic correction of MLL4 truncation mutation rescues the aberrant localization phenotype and restores multiple MLL4 regulatory functions, including COMPASS integrity and stabilization, histone H3K4 mono-methylation, enhancer activation, and gene regulation. Moreover, isogenic correction diminishes the sensitivity of MLL4-mutated cancer cells to targeted metabolic inhibition. Using immunohistochemistry (IHC), we id...
Source: GEO: Gene Expression Omnibus - December 5, 2023 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other Homo sapiens Source Type: research
Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D ‐related Kabuki syndrome
ConclusionsHearing characteristics of three individuals with three novel pathogenic variants ofKMT2D range from mild to profound fluctuating hearing loss with mild to moderate SNHL. HRCT scans showed that all three individuals had anatomical middle and inner ear abnormalities. KS 1 patients must get clinical therapy for OME, frequent auditory monitoring, and prompt intervention. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - November 4, 2023 Category: Genetics & Stem Cells Authors: Zhoushu Zheng,
Lu Ding,
Meihong Wang,
Yinghui Zhang,
Yihui Yang,
Ming Tang,
Jun Xu,
Liangjiong Wang,
Junhua Wu,
Haibo Li Tags: ORIGINAL ARTICLE Source Type: research
Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome
CONCLUSIONS: Hearing characteristics of three individuals with three novel pathogenic variants of KMT2D range from mild to profound fluctuating hearing loss with mild to moderate SNHL. HRCT scans showed that all three individuals had anatomical middle and inner ear abnormalities. KS 1 patients must get clinical therapy for OME, frequent auditory monitoring, and prompt intervention.PMID:37921229 | DOI:10.1002/mgg3.2306 (Source: Molecular Medicine)
Source: Molecular Medicine - November 3, 2023 Category: Molecular Biology Authors: Zhoushu Zheng Lu Ding Meihong Wang Yinghui Zhang Yihui Yang Ming Tang Jun Xu Liangjiong Wang Junhua Wu Haibo Li Source Type: research
Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome
CONCLUSIONS: Hearing characteristics of three individuals with three novel pathogenic variants of KMT2D range from mild to profound fluctuating hearing loss with mild to moderate SNHL. HRCT scans showed that all three individuals had anatomical middle and inner ear abnormalities. KS 1 patients must get clinical therapy for OME, frequent auditory monitoring, and prompt intervention.PMID:37921229 | DOI:10.1002/mgg3.2306 (Source: Molecular Medicine)
Source: Molecular Medicine - November 3, 2023 Category: Molecular Biology Authors: Zhoushu Zheng Lu Ding Meihong Wang Yinghui Zhang Yihui Yang Ming Tang Jun Xu Liangjiong Wang Junhua Wu Haibo Li Source Type: research
Peripheral blood DNA methylation and neuroanatomical responses to HDACi treatment that rescues neurological deficits in a Kabuki syndrome mouse model
Recent findings from studies of mouse models of Mendelian disorders of epigenetic machinery strongly support the potential for postnatal therapies to improve neurobehavioral and cognitive deficits. As several ... (Source: Clinical Epigenetics)
Source: Clinical Epigenetics - October 27, 2023 Category: Research Authors: Sarah Jessica Goodman, Teresa Romeo Luperchio, Jacob Ellegood, Eric Chater-Diehl, Jason P. Lerch, Hans Tomas Bjornsson and Rosanna Weksberg Tags: Research Source Type: research
Pulmonary hypertension — a novel phenotypic hypothesis of Kabuki syndrome: a case report and literature review
Pediatric pulmonary hypertension (PH) is a serious and rare disease that is often derived from genetic mutations. Kabuki syndrome (KS) is a chromosomal abnormality disease that has its origin in the mutation o... (Source: BMC Pediatrics)
Source: BMC Pediatrics - August 28, 2023 Category: Pediatrics Authors: Xiao-xian Deng, Bo-wen Jin, Shan-shan Li, Hong-mei Zhou, Qun-shan Shen and Yun-yan Li Tags: Case report Source Type: research
Treatment of immune thrombocytopenia with hetrombopag olamine tablets in a Kabuki syndrome patient with new KMT2D mutations
Platelets. 2023 Dec;34(1):2249562. doi: 10.1080/09537104.2023.2249562.ABSTRACTKabuki syndrome (KS) is a rare multisystem-affecting genetic disorder, and usually accompanied with autoimmune disorders such as immune thrombocytopenic purpura (ITP). Here, we report a 16-year-old patient with Kabuki syndrome with ITP and observe the therapeutic effect of TPO agonist hetrombopag olamine tablets. The duration of maintenance therapy and follow up were both 17 months. Whole exon sequencing (WES) of the patient's peripheral blood showed c.5775_5778del (p. Leu1926LysfsTer120) heterozygous mutation in the KMT2D gene, which was not rep...
Source: Platelets - August 24, 2023 Category: Hematology Authors: Peng Peng Ying Pan Xueqing Lu Hui Xu Ziwei Zhou Yuanqing He Huiru Wang Changcheng Zheng Li Zhou Source Type: research
