Journal of Shandong University (Health Sciences) ›› 2024, Vol. 62 ›› Issue (2): 90-95.doi: 10.6040/j.issn.1671-7554.0.2023.1041

• Clinical Medicine • Previous Articles    

A case of Kabuki syndrome caused by KMT2D gene mutation

DONG Jianing1,2, ZHANG Piaopiao1, XU Fenfen1, ZHAO Hongyang1   

  1. 1. Department of Pediatrics, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China;
    2. Shandong First Medical University/Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
  • Published:2024-03-29

PDF (PC)

39

Abstract: Objective To explore the clinical phenotype, gene variant types and diagnosis of genetic testing of Kabuki syndrome(KS). Methods The whole exon sequencing(WES)of peripheral blood of a child was performed and verified with Sanger DNA sequencing. Results The proband was a girl aged 6 years and 5 months, who showed special facial features, developmental delay, convulsive seizures, abnormal electroencephalogram, and recurrent otitis media. WES showed KMT2D gene(NM003482)c.3094del,(p.Leu1032TrpfsTer24)mutation, which was a frameshift mutation. Sanger DNA sequencing results showed that the father and mother of the proband did not carry the KMT2D mutation, indicating that this mutation was a de novo one. According to the(American College of Medical Genetics and Genomics, ACMG)mutation interpretation standard, the mutation was classified as PVS1+PS2+PM2, which was a pathogenic mutation of KS. Conclusion The child was diagnosed with KS type 1 caused by KMT2D gene mutation, which was autosomal dominant. Our study revealed that early diagnosis and intervention should be performed for suspected KS; for patients with no known genetic variation, clinical diagnosis should be confirmed according to international consensus criteria, follow-up and genetic counseling. This study enriched the genetic mutation spectrum of KS and provided a basis for the diagnosis and genetic counseling of this disease.

Key words: Kabuki syndrome, KMT2D gene, Special facial features, Trio-whole genome testing

CLC Number: 

  • R725
[1] Niikawa N, Matsuura N, Fukushima Y, et al. Kabuki make-up syndrome: a syndrome of mentalretardation, unusual facies, large and protruding ears, and postnatal growth deficiency[J]. J Pediatr, 1981, 99(4): 565-569.
[2] Kuroki Y, Suzuki Y, Chyo H, et al. A new malformation syndrome of long palpebralfissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation[J]. J Pediatr, 1981, 99(4): 570-573.
[3] Niikawa N, Kuroki Y, Kajii T, et al. Kabuki make-up(Niikawa-Kuroki)syndrome: a study of 62 patients[J]. Am J Med Genet, 1988, 31(3): 565-589.
[4] Adam M, Hudgins L. Kabuki syndrome: a review: Kabuki syndrome[J]. Clin Genet, 2004, 67(3): 209-219.
[5] Hoffman JD, Ciprero KL, Sullivan KE, et al. Immune abnormalities are a frequent manifestation of Kabuki syndrome[J]. Am J Med Genet A, 2005, 135A(3): 278-281.
[6] Adam MP, Banka S, Bjornsson HT, et al. Kabuki syndrome: international consensus diagnostic criteria[J]. J Med Genet, 2019, 56(2): 89-95.
[7] Ng SB, Bigham AW, Buckingham KJ, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome[J]. Nat Genet, 2010, 42(9): 790-793.
[8] Lederer D, Grisart B, Digilio MC, et al. Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with kabuki syndrome[J]. Am J Hum Genet, 2012, 90(1): 119-124.
[9] Lange L, Pagnamenta AT, Lise S, et al. A de novo frameshift in HNRNPK causing a Kabuki-like syndrome with nodular heterotopia: De novo frameshift in HNRNPK causing Kabuki-like syndrome with nodular heterotopia[J]. Clin Genet, 2016, 90(3): 258-262.
[10] Bögershausen N, Gatinois V, Riehmer V, et al. Mutation update for Kabuki syndrome genes KMT2D and KDM6A and further delineation of X-linked Kabuki syndrome subtype 2[J]. Hum Mutat, 2016, 37(9): 847-864.
[11] Froimchuk E, Jang Y, Ge K. Histone H3 lysine 4 methyltransferase KMT2D[J]. Gene, 2017, 627: 337-342. doi: 10.1016/j.gene.2017.06.056.
[12] Shilatifard A. Molecular implementation and physiological roles for histone H3 lysine 4(H3K4)methylation[J]. Curr Opin Cell Biol, 2008, 20(3): 341-348.
[13] Ortega-Molina A, Boss IW, Canela A, et al. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development[J]. Nat Med, 2015, 21(10): 1199-1208.
[14] Zhang J, Dominguez-Sola D, Hussein S, et al. Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis[J]. Nat Med, 2015, 21(10): 1190-1198.
[15] 郭宁, 吴方, 汪捷, 等. 利用CRISPR/Cas9技术构建KMT2D基因敲除的人胚胎干细胞系[J]. 生物技术, 2020, 30(3): 230-242. GUO Ning, WU Fang, WANG Jie, et al. Knocking out KMT2D in a human embryonic stem cell line using CRISPR/ Cas9 system[J]. Biotechnology, 2020, 30(3): 230-242.
[16] Kim SJ, Cho SY, Maeng SH, et al. A novel MLL2 gene mutation in a Korean patient with Kabuki syndrome[J]. Korean J Pediatr, 2013, 56(8): 355.
[17] Kurahashi N, Miyake N, Mizuno S, et al. Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations[J]. Brain Dev, 2017, 39(8): 672-677.
[18] Ogawa A, Yasumoto S, Tomoda Y, et al. Favorable seizure outcome in kabuki make-up syndrome associated with epilepsy[J]. J Child Neurol, 2003, 18(8): 549-551.
[19] Verrotti A, Agostinelli S, Cirillo C, et al. Long-term outcome of epilepsy in Kabuki syndrome[J]. Seizure, 2011, 20(8): 650-654.
[20] Lodi M, Chifari R, Parazzini C, et al. Seizures and EEG pattern in Kabuki syndrome[J]. Brain Dev, 2010, 32(10): 829-834.
[21] Musumeci SA, Hagerman RJ, Ferri R, et al. Epilepsy and EEG Findings in Males with Fragile X Syndrome[J]. Epilepsia, 1999, 40(8): 1092-1099.
[22] Bekircan-Kurt CE, ?瘙塁im?瘙塂ek-Kiper PÖ, Boduro glu K, et al. A novel de novo mutation involving the mll2 gene in a kabuki syndrome patient presenting with seizures[J]. Turk J Pediatr, 2016, 58(1): 97.
[23] Di Candia F, Fontana P, Paglia P, et al. Clinical heterogeneity of Kabuki syndrome in a cohort of Italian patients and review of the literature[J]. Eur J Pediatr, 2022, 181(1): 171-187.
[24] Lin JL, Lee WI, Huang JL, et al. Immunologic assessment and KMT2D mutation detection in Kabuki syndrome[J]. Clinical Genetics, 2015, 88(3): 255-260.
[25] 徐果, 吴泽斌, 李兰. 高危儿童分泌性中耳炎的诊疗策略[J]. 中华耳科学杂志, 2020, 18(5): 857-860. XU Guo, WU Zebin, LI Lan.Diagnostic and therapeutic strategies for otitis media with effusion in at-risk children[J]. Chinese Journal of Otology, 2020, 18(5): 857-860.
[26] Vesseur A, Cillessen E, Mylanus E. Cochlear implantation in a patient with Kabuki syndrome[J]. J Int Adv Otol, 2016, 12(1): 129-131.
[27] Goldmuntz E. 22q11.2 deletion syndrome and congenital heart disease[J]. Am J Med Genet C Semin Med Genet, 2020, 184(1): 64-72.
[28] Biard JM, Payrat S, Clapuyt P, et al. Antenatal diagnosis of CHARGE syndrome: Prenatal ultrasound findings and crucial role of fetal dysmorphic signs. About a series of 10 cases and review of literature[J]. Eur J Med Genet, 2021, 64(4): 104189.
[29] 代晓微, 郑连文, 徐影, 等. 一例歌舞伎化妆综合征(Kabuki Syndrome)患儿的病例及遗传学分析[J]. 中国优生与遗传杂志, 2018, 26(2): 85-86, 70.
[1] ZHANG Amin, LI Guosheng, LI Fuhai. Bronchoalveolar lavage fluid cytokine profile contributes to discriminating local inflammation in children with mycoplasma lobar pneumonia [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 82-88.
[2] . [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 125-128.
[3] ZHANG Qian, QIN Mingming, HE Xuejia, CAI Qiujing, ZHANG Yamin, LI Qingsu, ZHU Weiwei. Effects of calcitriol on EMT induced by TGF-β1 in asthma [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 10-18.
[4] YANG Liping, MU Tingting, YANG Yujuan, ZHANG Yu, SONG Xicheng. Effects of inhaled allergens on pulmonary function in children with adenoid hypertrophy complicated with bronchial asthma [J]. Journal of Shandong University (Health Sciences), 2020, 58(3): 107-112.
[5] KAN Nana, YU Lichun, SUN Shuzhen, LI Qian, LUAN Chunli. Clinics, pathology and prognosis of 30 children with nephrotic syndrome in clinical trials of lupus nephritis [J]. Journal of Shandong University (Health Sciences), 2020, 58(2): 54-59.
[6] ZHAO Lijian, HAN Bo, ZHANG Jianjun, YI Yingchun, JIANG Diandong, LÜ Jianli, WANG Jing. Feasibility and safety of transcatheter closure of ventricular septal defect with subaortic rim <2 mm [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(8): 52-56.
[7] LI Xue, LI Dong, SHI Qing, ZHOU Panpan, JU Xiuli. Expression and role of Helios gene in regulatory T cells of pediatric precursor B-cell acute lymphoblastic leukemia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(4): 76-81.
[8] CHENG Xiangdeng, LIANG Shuang, HU Yanyan, QIAO Yu, WANG Fengxue, LI Guimei. Hypothalamic-pituitary-gland axis function changes and metabolic manifestations of children with Prader-Willi syndrome [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(3): 107-111.
[9] LIU Mengmeng, ZHAO Cuifen, KONG Qingyu, CAI Zhifeng, XIA Wei. miR-1/133 participates in the expression of ion channel genes of myocardial cells in myocarditis mice [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(8): 6-11.
[10] XU Tianyi, WU Ping, WANG Ailing, CHEN Liping. Clinical effect of milrinone atomization inhalation on treating severe pneumonia complicated with heart failure of neonates and infants [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(7): 88-90.
[11] ZHU Jing, GUO Aili, ZHANG Nan, QIN Mingming, LIU Lijuan, ZHU Weiwei. Effect of erythropoietin on hypoxic ischemic encephalopathy in neonates [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(4): 60-63.
[12] LI Yan, WANG Yi, QIAO Xiuyun, ZHANG Li, SUN Jin. Effect of resistin with different levels on serum free fatty acid [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(11): 6-9.
[13] LI Yuanyuan, ZHANG Nan, XU Mi, QIN Mingming, DOU Dongdong, ZHU Weiwei. Expression of stromal cell derived factor-1α and its effects in hypoxic-ischemic brain tissue of neonatal mice [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(10): 26-31.
[14] ZHAO Hui-ling, DU Xi-xia, ZHANG Hai-rong, LIU Jian-hua, YANG Hui-rong. Analysis of characteristics of allergen skin prick test in children with allergic disease in Shijiazhuang region [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(Z1): 150-151.
[15] DU Qingxia, LI Fuhai, ZHAO Cuifen, KONG Qingyu, HUANG Xiaoyang, XIA Wei. Early effect of shear stress on the apoptosis of pulmonary microvascular endothelial cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(10): 9-14.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd