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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2018

Open Access 01-12-2018 | Case report

Novel KDM6A splice-site mutation in kabuki syndrome with congenital hydrocephalus: a case report

Authors: Zhimei Guo, Fang Liu, Hai Jun Li

Published in: BMC Medical Genetics | Issue 1/2018

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Abstract

Background

Kabuki syndrome (KS) is a rare congenital anomaly syndrome affecting multiple organs. Two genes have been shown to be mutated in patients with KS: lysine (K)-specific demethylase 6A (KDM6A) and lysine (K)-specific methyltransferase 2D (KMT2D, formerly MLL2). Although the congenital clinical characteristic is helpful in diagnosis of the KS, there are no reports of specific findings in fetuses that might suggest the syndrome prenatally.

Case presentation

In this study, we described a male patient with a novel KDM6A splicing in exon(exon4) and flanking intron(intron3)-exon boundaries characterized by congenital hydrocephalus which had never been reported before. The male patient had inherited the c.335-1G > T splice site mutation from his mother who had fewer dysmorphic features than the patient who displayed a more severe phenotype with multiple organ involvement. Our research suggests that congenital hydrocephalus may accompany KS type 2, which improve the knowledge on KS further more.

Conclusions

Based on genetic and clinical features, suggest that the c.335-1G > T splicing mutation in KDM6A causing KS-2 disease. At least for this case, we suggest that congenital hydrocephalus is closely associated with KS type 2.
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Literature
1.
Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr. 1981;99(4):565–9.CrossRefPubMed
2.
Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr. 1981;99(4):570–3.CrossRefPubMed
3.
Van Laarhoven PM, Neitzel LR, Quintana AM, Geiger EA, Zackai EH, Clouthier DE, Artinger KB, Ming JE, Shaikh TH. Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development. Hum Mol Genet. 2015;24(15):4443–53.CrossRefPubMedPubMedCentral
4.
Lindsley AW, Saal HM, Burrow TA, Hopkin RJ, Shchelochkov O, Khandelwal P, Xie C, Bleesing J, Filipovich L, Risma K, et al. Defects of B-cell terminal differentiation in patients with type-1 kabuki syndrome. J Allergy Clin Immunol. 2016;137(1):179–87.CrossRefPubMed
5.
Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, et al. Exome sequencing identifies MLL2 mutations as a cause of kabuki syndrome. Nat Genet. 2010;42(9):790–3.CrossRefPubMedPubMedCentral
6.
Lederer D, Grisart B, Digilio MC, Benoit V, Crespin M, Ghariani SC, Maystadt I, Dallapiccola B, Verellen-Dumoulin C. Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with kabuki syndrome. Am J Hum Genet. 2012;90(1):119–24.CrossRefPubMedPubMedCentral
7.
Bögershausen N, Gatinois V, Riehmer V, Kayserili H, Becker J, Thoenes M, Simsek-Kiper PÖ, Barat-Houari M, Elcioglu NH, Wieczorek D, et al. Mutation update for kabuki syndrome genes KMT2D and KDM6A and further delineation of X-linked kabuki syndrome subtype 2. Hum Mutat. 2016;37(9):847–64.CrossRefPubMed
8.
Niikawa N, Kuroki Y, Kajii T, Matsuura N, Ishikiriyama S, Tonoki H, Ishikawa N, Yamada Y, Fujita M, Umemoto H, et al. Kabuki make-up (Niikawa-Kuroki) syndrome: A study of 62 patients. Am J Med Genet. 1988;31(3):565–89.CrossRefPubMed
9.
Banka S, Veeramachaneni R, Reardon W, Howard E, Bunstone S, Ragge N, Parker MJ, Crow YJ, Kerr B, Kingston H, et al. How genetically heterogeneous is kabuki syndrome?: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum. Eur J Hum Genet. 2012;20(4):381–8.CrossRefPubMed
10.
Miyake N, Koshimizu E, Okamoto N, Mizuno S, Ogata T, Nagai T, Kosho T, Ohashi H, Kato M, Sasaki G, et al. MLL2 and KDM6A mutations in patients with kabuki syndrome. Am J Med Genet A. 2013;161A(9):2234–43.CrossRefPubMed
11.
Miyake N, Mizuno S, Okamoto N, Ohashi H, Shiina M, Ogata K, Tsurusaki Y, Nakashima M, Saitsu H, Niikawa N, et al. KDM6A point mutations cause kabuki syndrome. Hum Mutat. 2013;34(1):108–10.CrossRefPubMed
12.
Lederer D, Shears D, Benoit V, Verellen-Dumoulin C, Maystadt I. A three generation X-linked family with kabuki syndrome phenotype and a frameshift mutation in KDM6A. Am J Med Genet. 2014;164A(5):1289–92.CrossRefPubMed
13.
WHO. Child growth standards. Geneva: WHO; 2006. Available: http://​www.​who.​int/​childgrowth/​ standards/en/
14.
Long A, Sinkovskaya ES, Edmondson AC, Zackai E, Schrier Vergano SA. Kabuki syndrome as a cause of non-immune fetal hydrops/ascites. Am J Med Genet A. 2016;170(12):3333–7.CrossRefPubMed
15.
Kasuya H, Shimizu T, Nakamura S, Takakura K. Kabuki make-up syndrome and report of a case with hydrocephalus. Childs Nerv Syst. 1998;14(6):230–5.CrossRefPubMed
16.
Micale L, Augello B, Maffeo C, Selicorni A, Zucchetti F, Fusco C, De Nittis P, Pellico MT, Mandriani B, Fischetto R, et al. Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of kabuki syndrome patients. Hum Mutat. 2014;35(7):841–50.CrossRefPubMedPubMedCentral
17.
Banka S, Lederer D, Benoit V, Jenkins E, Howard E, Bunstone S, Kerr B, McKee S, Lloyd IC, Shears D, et al. Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked kabuki syndrome (KS2). Clin Genet. 2015;87(3):252–8.CrossRefPubMed
18.
Welstead GG, Creyghton MP, Bilodeau S, Cheng AW, Markoulaki S, Young RA, Jaenisch R. X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc Natl Acad Sci U S A. 2012;109(32):13004–9.CrossRefPubMedPubMedCentral
Metadata
Title
Novel KDM6A splice-site mutation in kabuki syndrome with congenital hydrocephalus: a case report
Authors
Zhimei Guo
Fang Liu
Hai Jun Li
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-018-0724-4

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