Abstract This article reports the clinical and genetic features of a case of Tatton-Brown-Rahman syndrome (TBRS) caused by DNMT3A gene mutation. A girl, aged 8 months and 14 days, had the clinical manifestations of psychomotor retardation, hypotonia, ventricular enlargement, and tonsillar hernia malformation. Gene analysis identified a novel heterozygous mutation, c.134C > T(p.A45V), in the DNMT3A gene, and the wild type was observed at this locus in her parents. This mutation was determined as a possible pathogenic mutation according to the guidelines of American College of Medical Genetics and Genomics, which had not been reported in previous studies and conformed to autosomal dominant inheritance. This child was diagnosed with TBRS. TBRS often has a good prognosis, with overgrowth and mental retardation as the most common clinical manifestations, and behavioral and psychiatric problems, scoliosis, and afebrile seizures are possible complications of TBRS. The possibility of TBRS should be considered for children with overgrowth and mental retardation, and genetic diagnosis should be conducted when necessary.
CHEN Min,LI Si-Tao,CAI Yao et al. Tatton-Brown-Rahman syndrome associated with the DNMT3A gene: a case report and literature review[J]. CJCP, 2020, 22(10): 1114-1118.
CHEN Min,LI Si-Tao,CAI Yao et al. Tatton-Brown-Rahman syndrome associated with the DNMT3A gene: a case report and literature review[J]. CJCP, 2020, 22(10): 1114-1118.
Tatton-Brown K, Seal S, Ruark E, et al. Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability[J]. Nat Genet, 2014, 46(4):385-388.
[2]
Tatton-Brown K, Zachariou A, Loveday C, et al. The Tatton-Brown-Rahman syndrome:a clinical study of 55 individuals with de novo constitutive DNMT3A variants[J]. Wellcome Open Res, 2018, 3:46.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5):405-424.
[5]
Okamoto N, Toribe Y, Shimojima K, et al. Tatton-Brown-Rahman syndrome due to 2p23 microdeletion[J]. Am J Med Genet A, 2016, 170A(5):1339-1342.
[6]
Tlemsani C, Luscan A, Leulliot N, et al. SETD2 and DNMT3A screen in the Sotos-like syndrome French cohort[J]. J Med Genet, 2016, 53(11):743-751.
[7]
Lemire G, Gauthier J, Soucy JF, et al. A case of familial transmission of the newly described DNMT3A-overgrowth syndrome[J]. Am J Med Genet A, 2017, 173(7):1887-1890.
[8]
Hollink IHIM, van den Ouweland AMW, Beverloo HB, et al. Acute myeloid leukaemia in a case with Tatton-Brown-Rahman syndrome:the peculiar DNMT3A R882 mutation[J]. J Med Genet, 2017, 54(12):805-808.
[9]
Kosaki R, Terashima H, Kubota M, et al. Acute myeloid leukemia-associated DNMT3A p.Arg882His mutation in a patient with Tatton-Brown-Rahman overgrowth syndrome as a constitutional mutation[J]. Am J Med Genet A, 2017, 173(1):250-253.
[10]
Jeffries AR, Maroofian R, Salter CG, et al. Growth disrupting mutations in epigenetic regulatory molecules are associated with abnormalities of epigenetic aging[J]. Genome Res, 2019, 29(7):1057-1066.
[11]
Shen W, Heeley JM, Carlston CM, et al. The spectrum of DNMT3A variants in Tatton-Brown-Rahman syndrome overlaps with that in hematologic malignancies[J]. Am J Med Genet A, 2017, 173(11):3022-3028.
[12]
Xin B, Cruz Marino T, Szekely J, et al. Novel DNMT3A germline mutations are associated with inherited Tatton-Brown-Rahman syndrome[J]. Clin Genet, 2017, 91(4):623-628.
[13]
Sweeney KJ, Mottolese C, Belot A, et al. The first case report of medulloblastoma associated with Tatton-Brown-Rahman syndrome[J]. Am J Med Genet A, 2019, 179(7):1357-1361.
[14]
Tatton-Brown K, Loveday C, Yost S, et al, et al. Mutations in epigenetic regulation genes are a major cause of overgrowth with intellectual disability[J]. Am J Hum Genet, 2017, 100(5):725-736.
[15]
Zhang W, Xu J. DNA methyltransferases and their roles in tumorigenesis[J]. Biomark Res, 2017, 5:1.
[16]
Uysal F, Akkoyunlu G, Ozturk S. Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos[J]. Biochimie, 2015, 116:103-113.
[17]
Lyko F. The DNA methyltransferase family:a versatile toolkit for epigenetic regulation[J]. Nat Rev Genet, 2018, 19(2):81-92.
[18]
Heyn P, Logan CV, Fluteau A, et al. Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of polycomb-regulated regions[J]. Nat Genet, 2019, 51(1):96-105.
[19]
Wu H, Coskun V, Tao J, et al. Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes[J]. Science, 2010, 329(5990):444-448.
[20]
Challen GA, Sun D, Jeong M, et al. Dnmt3a is essential for hematopoietic stem cell differentiation[J]. Nat Genet, 2011, 44(1):23-31.
[21]
Jeong M, Park HJ, Celik H, et al. Loss of Dnmt3a immortalizes hematopoietic stem cells in vivo[J]. Cell Rep, 2018, 23(1):1-10.
[22]
Yan XJ, Xu J, Gu ZH, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia[J]. Nat Genet, 2011, 43(4):309-315.
[23]
Nikoloski G, van der Reijden BA, Jansen JH. Mutations in epigenetic regulators in myelodysplastic syndromes[J]. Int J Hematol, 2012, 95(1):8-16.
[24]
Abdel-Wahab O, Levine RL. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia[J]. Blood, 2013, 121(18):3563-3572.
ZHANG Ji-Yong, ZHOU Shao-Ming, WANG Shao-Hua, SUI Feng-Xuan, GAO Wu-Hong, LIU Qing, CAI Hua-Bo, JIANG Hong-Ying, LI Wei-Yan, WANG Li-Ting, LI Li, ZHAO Wei, YING Jing, WU Qian-Zhen, WENG Bi-Xia, ZENG Yong-Mei. Risk factors for cow's milk protein allergy in infants: a multicenter survey[J]. CJCP, 2020, 22(1): 42-46.
