A case report of Kabuki syndrome with infantile spasm and literature review / 解放军医学杂志

Objective Through literature review to retrospectively study the clinical characteristics, treatment and prognosis of Kabuki syndrome with infantile spasm. Methods The clinical data of a case of Kabuki syndrome with infantile spasm hospitalized at the first medical center of Chinese PLA General Hospital in August 2019 were retrospectively analyzed, search on PubMed, CNKI, Wanfang Medical Online and online Mendelian Inheritance in Man (OMIM), to summarize the clinical data of Kabuki syndrome with infantile spasm and to explore its relationship with genotypes. Results A boy, 1 year and 7 months old, was admitted for "growth lag, intermittent convulsions for more than 1 year and 1 month". His growth and development were generally backward, had microcephaly, short stature and spasms, magnetic resonance imaging of brain showed normal, the thyroid hormone and growth hormone levels were normal, genetic analysis revealed a denovo frameshift mutation in KDM6A gene (c.2170-c.2171 delAT, p.I724Ifs∗5), electroencephagram showed hypsarrhuthmia, with a series of convulsions, diagnosed as "infantile spasm; Kabuki syndrome", after treating with ACTH, the spasms was completely controlled, multiple reexamination of EEG significantly improved. A total of 16 English literatures and 1 Chinese literature were obtained. There were 48 children had been diagnosed as Kabuki syndrome with epilepsy, including 6 children as Kabuki syndrome and infantile spasm. Among the above 6 cases, only 2 genetic test results were reported, 1 was missense mutation of KMT2D gene (c.96c >G, p.apsp32glu), and 1 was frameshift mutation of KDM6A gene (c.2515_2518del, p.apsn839valfs). Conclusion The new frameshift mutation of KDM6A gene (c.2170-c.2171delAT) in this child could lead to infantile spasm of Kabuki syndrome. Kabuki syndrome could be associated with infantile spasms. If spasm occurs and accompanied by a special face, Kabuki syndrome needs to be considered, gene sequencing should be performed if necessary, early treatment can completely control infantile spasms in all children with Kabuki syndrome, the abnormal of EEG could back to normal, will have a favorable prognosis.

Targeted Downregulation of kdm4a Ameliorates Tau-engendered Defects in Drosophila melanogaster

BACKGROUND: Tauopathies, a class of neurodegenerative diseases that includes Alzheimer's disease (AD), are characterized by the deposition of neurofibrillary tangles composed of hyperphosphorylated tau protein in the human brain. As abnormal alterations in histone acetylation and methylation show a cause and effect relationship with AD, we investigated the role of several Jumonji domain-containing histone demethylase (JHDM) genes, which have yet to be studied in AD pathology. METHODS: To examine alterations of several JHDM genes in AD pathology, we performed bioinformatics analyses of JHDM gene expression profiles in brain tissue samples from deceased AD patients. Furthermore, to investigate the possible relationship between alterations in JHDM gene expression profiles and AD pathology in vivo, we examined whether tissue-specific downregulation of JHDM Drosophila homologs (kdm) can affect tauR406W-induced neurotoxicity using transgenic flies containing the UAS-Gal4 binary system. RESULTS: The expression levels of JHDM1A, JHDM2A/2B, and JHDM3A/3B were significantly higher in postmortem brain tissue from patients with AD than from non-demented controls, whereas JHDM1B mRNA levels were downregulated in the brains of patients with AD. Using transgenic flies, we revealed that knockdown of kdm2 (homolog to human JHDM1), kdm3 (homolog to human JHDM2), kdm4a (homolog to human JHDM3A), or kdm4b (homolog to human JHDM3B) genes in the eye ameliorated the tauR406W-engendered defects, resulting in less severe phenotypes. However, kdm4a knockdown in the central nervous system uniquely ameliorated tauR406W-induced locomotion defects by restoring heterochromatin. CONCLUSION: Our results suggest that downregulation of kdm4a expression may be a potential therapeutic target in AD.

Research progress of histone lysine demethylase KDM5A in tumors / 肿瘤

Histone methylation is one of the important research contents of epigenetics. Methylation of histones is dynamically regulated by histone methylase and histone demethylase. Histone lysine (K) demethylase 5A (KDM5A) is an important member in the histone demethylase family, which can specifically remove the dimethyl and trimethyl from the 4th lysine of histone H3 (H3K4me2/3), thus mediating gene silencing and regulating cell function. KDM5A can directly or indirectly maintain tumor cell dryness, inhibit cell metabolism and differentiation, promote tumor cell proliferation, metastasis and drug resistance, so it is closely related to the occurrence, development and drug resistance of various tumors. KDM5A may become a new potential target for the diagnosis and treatment of tumors.

Correlation between the expression of JARID1B/KDM5B in breast cancer tissues and the circulating tumor cells / 基础医学与临床

Objective To investigate the relation between expression of JARID1B/KDM5B in invasive breast cancer tissue and circulating tumor cells of invasive breast patients. Methods The S-P immunohistochemical method was used to observe the expression of JARID1B/KDM5B in lesions.imFISH method was used to detect circulation tumor cells. Results Twenty-seven cases of patients showed CTC positive(the number of CTC was more than or equal to 2) in 35 invasive breast cancer cases,The results of JARID1B/KDM5B expression were as follows:(-) (n=0) and (+) in 1 case,(++) in 3 cases,(+++) in 23 cases,8 cases of negative cases (the number of CTC < 2), JARID1B/KDM5B immune group of results:(-) (n=2),(+) in 2 cases,(++) in 1 case,(+++) in 3 cases, The positive relation was found in expression of JARID1B/KDM5B and circulating tumor cells(P<0.05). Conclu-sions JARID1B/KDM5B positive expression in tumor tissues has a certain significance in predicting the recurrence and metastasis of tumor.

Diagnosis and treatment of Kabuki syndrome and its recent progress in molecular mechanisms / 国际儿科学杂志

Kabuki syndrome(KS),also called kabuki make-up syndrome,is characterized by backward growth retardation,skeletal developmental delay,major facial dysmorphic features,multi-organ abnormalities and abnormal dermatoglyphic pattern and mild or moderate mental retardation.For the molecular genetic pathogenesis of KS,KTM2D and KDM6A gene mutations have been identified as pathogenic genes of KS,which regulate the gene expression through chromatin remodelling and histone modification.At present,the etiology and pathogenesis of KS are still unknown.There is no useful biochemical index and standard radiographic findings for the diagnosis of KS.Molecular genetic diagnosis is still to be explored.Currently,the diagnosis of KS is mainly based on five cardinal manifestations:a peculiar face,skeletal anomalies,dermatoglyphic abnormalities,mild to moderate mental retardation and postnatal growth deficiency.For these patients,it can reach a better prognosis the by clinical early detection,early diagnosis,early intervention,as well as improving the growth level,symptomatic treatment,active prevention and treatment of complications as far as possible.

Differential expression of histone demethylase KDM3B and JMJD1C in acute myeloid leukemia / 中国生化药物杂志

Objective To investigate the synergistic regulation of KDM3B and JMJD1C in leukemia. Methods The expression level of JMJD1C and KDM3B were analyzed in multiple acute myeloid leukemia (AML) cell lines. AML cell lines NB4 and HL-60 were treated with Daminozide, followed by determination of H3K9 mono-methylation and di-methylation. AML cell lines NB4 and HL-60 were treated with Daminozide, ATRA (retinoid acid All-trans), C Vitamin and the expression of KDM3B and JMJD1C were detected by real-time quantitative PCR. Results The expression level of KDM3B and JMJD1C in the AML cell lines was negatively correlated. In NB4 and HL-60 cells treated by daminozide, H3K9 mono-methylation and di- methylation level showed a rising trend in these two cell groups. After treatment of NB4 cells with the 3 reagents, the level of mRNA of KDM3B was down-regulated while the level of mRNA of JMJD1C was up-regulated. In HL-60 cells treated by daminozide, the mRNA level of KDM3B was up-regulated and the mRNA level of JMJD1C was down-regulated. Conclusion The expression of KDM3B and JMJD1C is negatively correlated in patients with AML.

Síndrome de Kabuki: presentación de un Caso y Revisión de la Literatura / Kabuki Syndrome: A case report and literature review

Resumen El síndrome de Kabuki (SK) es una patología muy rara, descrita por primera vez en 1981 por Niikawa y Kuroki en Japón. Se han publicado cerca de 400 casos a nivel mundial. En Colombia se conocen cinco casos diagnosticados y publicados; el caso objeto de este estudio sería el sexto en nuestro país. Presentamos la descripción del caso de una paciente de 2 años y 6 meses con rasgos dismórficos compatibles con síndrome de Kabuki. Examen físico: fisuras palpebrales elongadas, eversión del tercio lateral párpado inferior, cejas arqueadas con tercio lateral más despoblado, puente nasal deprimido, boca en carpa, paladar hendido, pabellones auriculares de baja implantación con rotación posterior. El síndrome de Kabuki se caracteriza por sus anomalías faciales peculiares que se consideran son la única manifestación que puede orientar al diagnóstico del mismo sin excepciones. Recientemente se han identificado mutaciones sin sentido y de corrimiento del marco de lectura, entre otras en el gen MLL2 en aproximadamente el 75 % de los casos y en una menor proporción deleciones y mutaciones sin sentido en el gen KDM6A.

Abstract Kabuki syndrome is a rare disease described by Kuroki and Niikawa in Japanese population in 1981. There are over 400 cases over the world and 5 cases described in Colombian population. Therefore this is the 6th Kabuki syndrome found in Colombia. We report a 2 years old female with Kabuki syndrome phenotype. Clinical examination showed: long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, left palate and low setup ears. Kabuki syndrome includes facial features whit specific characteristics enough to classify the patients. However, there are some mutations in MLL2 gene present in almost 75 % of Kabuki syndrome. In addition there are some deletion and duplications abnormalities in KMD6A gene described in Kabuki syndrome patients.

Kabuki syndrome: clinical and molecular characteristics / 소아과

Kabuki syndrome (KS) is a rare syndrome characterized by multiple congenital anomalies and mental retardation. Other characteristics include a peculiar facial gestalt, short stature, skeletal and visceral abnormalities, cardiac anomalies, and immunological defects. Whole exome sequencing has uncovered the genetic basis of KS. Prior to 2013, there was no molecular genetic information about KS in Korean patients. More recently, direct Sanger sequencing and exome sequencing revealed KMT2D variants in 11 Korean patients and a KDM6A variant in one Korean patient. The high detection rate of KMT2D and KDM6A mutations (92.3%) is expected owing to the strict criteria used to establish a clinical diagnosis. Increased awareness and understanding of KS among clinicians is important for diagnosis and management of KS and for primary care of KS patients. Because mutation detection rates rely on the accuracy of the clinical diagnosis and the inclusion or exclusion of atypical cases, recognition of KS will facilitate the identification of novel mutations. A brief review of KS is provided, highlighting the clinical and genetic characteristics of patients with KS.

A novel MLL2 gene mutation in a Korean patient with Kabuki syndrome / 소아과

Kabuki syndrome (KS) is a rare genetic disease with a distinctive dysmorphic face, intellectual disability, and multiple congenital abnormalities. KS is inherited in an autosomal dominant manner. As the primary cause of KS, MLL2 mutations have been identified in 56-76% of affected individuals who have been tested, suggesting that there may be additional genes associated with KS. Recently, a few KS individuals have been found to have de novo partial or complete deletions of an X chromosome gene, KDM6A, which encodes a histone demethylase that interacts with MLL2. Nevertheless, mutations in MLL2 are the major cause of KS. Although there are a few reports of KS patients in Korea, none of these had been confirmed by genetic analysis. Here, we report a case of a Korean patient with clinical features of KS. Using direct sequencing, we identified a frameshift heterozygous mutation for MLL2: (c.5256_5257delGA;p.Lys1753Alafs*34). Clinically, the patient presented with typical facial features, and diagnosis of KS was based on the diagnostic criteria. While KS is a rare disease, other malformations that overlap with those found in individuals with KS are common. Hence, the diagnosis of KS by mutational analysis can be a valuable method for patients with KS-like syndromes. Furthermore, in the near future, other genes could be identified in patients with KS without a detectable MLL2 mutation.