Journal of Shandong University (Health Sciences) ›› 2020, Vol. 58 ›› Issue (4): 105-109.doi: 10.6040/j.issn.1671-7554.0.2019.1529

Previous Articles    

A case of syndromic neurodevelopmental disorder caused by heterozygous mutation in EBF3

LIU Na1, LIU Qiji2, MOU Kai1, CHENG Cuiyun1   

  1. 1. Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo 255000, Shandong, China;
    2. Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Basic Medical Sciences, Jinan, Shandong, 250012, China
  • Published:2022-09-27

PDF (PC)

231

Abstract: Objective To explore the genetic basis of an infant with global developmenfal delay, mental retardation,hypotonia and ataxia. Methods The clinical phenotypes of the infant were analyzed. Peripheral blood samples were collected from the infant and his parents. The infant blood sample underwent G-banding chromosome analysis and SNP-array. The infant and his parents’ blood samples underwent whole exome sequencing. The pathogenicity of mutation sites was analyzed with bioinformatics. Results The G-band chromosome analysis and SNP-array of the infant showed no pathogenic mutation. The whole exome sequencing revealed that there was a heterozygous mutation of EBF3 c.626G>A(p.Arg209Gln)in the infant, which was validated by Sanger sequencing, but the parents had no such mutation. Conclusion The heterozygous mutation of EBF3 c.626G>A(p.Arg209Gln)probably underlies the disorder in the infant, which has not been reported in China.

Key words: Hypotonia, ataxia and delayed development syndrome, Whole exome sequencing, EBF3 gene, Gene mutation

CLC Number: 

  • R596.2
[1] Sleven H, Welsh SJ, Yu J, et al. De novo mutations in EBF3 cause a neurodevelopmental syndrome [J]. Am J Hum Genet, 2017, 100(1): 138-150.
[2] Zardo G, Tiirikainen MI, Hong C, et al. Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumors [J]. Nat Genet, 2002, 32(3): 453-458.
[3] Lopes F, Soares G, Goncalves-Rocha M, et al. Whole gene deletion of EBF3 supporting haploinsufficiency of this gene as a mechanism of neurodevelopmental disease[J]. Front Genet, 2017, 8: 143. doi: 10.3389/fgene.2017.00143. eCollection 2017.
[4] Chao HT, Davids M, Burke E, et al. A syndromic neurodevelopmental disorder caused by de novo variants in EBF3[J]. Am J Hum Genet, 2017, 100(1): 128-137.
[5] Blackburn PR, Barnett SS, Zimmermann MT, et al.Novel de novo variant in EBF3 is likely to impact DNA binding in a patient with a neurodevelopmental disorder and expanded phenotypes: patient report, in silico functional assessment, and review of published cases [J]. Cold Spring Harb Mol Case Stud, 2017, 3(3): a001743. doi:10.1101/mcs.a001743.
[6] Tanaka AJ, Cho MT, Willaert R, et al. De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism[J]. Cold Spring Harb Mol Case Stud, 2017, 3(6). pii: a002097. doi: 10.1101/mcs.a002097.
[7] Harms FL, Girisha KM, Hardigan AA, et al. Mutations in EBF3 disturb transcriptional profiles and cause intellectual disability, ataxia, and facial dysmorphism [J]. Am J Hum Genet, 2017, 100(1): 117-127.
[8] Friocourt G, Parnavelas JG. Identification of Arx targets unveils new candidates for controlling cortical interneuron migration and differentiation [J]. Front Cell Neurosci, 2011, 27, 5: 28. doi: 10.3389/fnbeh.2011.00028.
[9] Prasad BC, Ye B, Zackhary R, et al.unc-3, a gene required for axonal guidance in Caenorhabditis elegans, encodes a member of the O/E family of transcription factors[J]. Development, 1998, 125(8): 1561-1568.
[10] Hattori Y, Usui T, Satoh D, et al. Sensory-neuron subtype-specific transcriptional programs controlling dendrite morphogenesis: genome-wide analysis of abrupt and Knot/Collier [J]. Dev Cell, 2013, 27(5): 530-544.
[11] Wang SS, Lewcock JW, Feinstein P, et al. Genetic disruptions of O/E2 and O/E3 genes reveal involvement in olfactory receptor neuron projection[J]. Development, 2004, 131(6): 1377-1388.
[12] Jin S, Kim J, Willert T, et al. Ebf factors and MyoD cooperate to regulate muscle relaxation via Atp2a1 [J]. Nat Commun, 2014, 5: 3793. doi: 10.1038/ncomms4793.
[13] Faria AC, Rabbi-Bortolini E, Reboucas M, et al. Craniosynostosis in 10q26 deletion patients: A consequence of brain underdevelopment or altered suture biology [J] Am J Med Genet A, 2016, 170A(2): 403-409.
[14] Liberg D, Sigvardsson M, Akerblad P. The EBF/Olf/Collier family of transcription factors: regulators of differentiation in cells originating from all three embryonal germ layers [J]. Mol Cell Biol, 2002, 22(24): 8389-8397.
[15] Siponen MI, Wisniewska M, Lehtio L, et al. Structural determination of functional domains in early B-cell factor(EBF)family of transcription factors reveals similarities to Rel DNA-binding proteins and a novel dimerization motif[J]. J Biol Chem, 2010, 285(34): 25875-25879.
[16] Fulp CT, Cho G, Marsh ED, et al. Identification of Arx transcriptional targets in the developing basal forebrain[J]. Hum Mol Genet, 2008, 17(23): 3740-3760.
[17] Alwan A, Modell B. Recommendations for introducing genetics services in developing countries[J]. Nat Rev Genet, 2003, 4(1): 61-68.
[18] de Ligt J, Willemsen MH, van Bon BW, et al. Diagnostic exome sequencing in persons with severe intellectual disability[J]. N Engl J Med, 2012, 367(20): 1921-1929.
[19] Zhu X, Petrovski S, Xie P, et al. Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios[J]. Genet Med, 2015, 17(10): 774-781.
[1] PAN Pengfei, XU Lisheng, JI Kunqian, WANG Dexiang, LI Yu. Mitochondrial myopathy beginning with respiratory failure: one case and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 54-59.
[2] Benkang SHI,Shouzhen CHEN,Sifeng QU,Yong WANG,Lei LIU. Research progress and clinical characteristics of clinical rapidly progressing prostate cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 110-116.
[3] SUN Yu, CHEN Na, MA Aihua. A case of congenital disorder of glycosylation caused by SLC35A2 gene mutation [J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 113-116.
[4] HUANG Xiuli, LIU Bingju, SUN Lifeng. Activated phosphoinositide 3-kinase δ syndrome caused by a mutation in PIK3CD gene: a case report and literature review [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 107-112.
[5] WANG Zhengyang, XIA Yan, SHI Kaixuan, TAO Kun, WANG Xiaojie. Effects of Trametinib on PAX8 expression in ovarian cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(10): 23-29.
[6] HU Sicui, SUN Qing, WANG Yibing, SUN Lili, SUI Yanxi, LI Tang. Analysis of CLCNKB gene mutation in two families with Bartter syndrome [J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 64-70.
[7] FENG Alei, DONG Qing, PANG Jiaohui, YIN Jiani, LI Qiang, HAN Junqing, YANG Zhe. Exploring molecular characteristics of esophageal squamous cell carcinoma based on next-generation sequencing [J]. Journal of Shandong University (Health Sciences), 2019, 57(7): 80-85.
[8] DING Tingting, ZOU Dong, LIU Haochen. An analysis of the mutation of MSX1 gene in a non-syndromic tooth agenesis family [J]. Journal of Shandong University (Health Sciences), 2019, 57(4): 97-100.
[9] DOU Chunhui, SHAO Jianhua, DONG Xuebin, ZHANG Ling, CHEN Ping, ZHAO Hongyu, GU Linping, SUN Lin, XIE Jie, WANG Min, WANG Juan, LI Na, LI Fan, LI Daqi. Effect of gene mutation on the clinical efficacy of decitabine for patients with myelodysplastic syndrome [J]. Journal of Shandong University (Health Sciences), 2019, 57(3): 42-48.
[10] ZHANG Wenhui, CHEN Yun, CHANG Yali, ZHOU Yawei, FANG Yunhai, ZHANG Xinsheng, GUO Nongjian. Gene detection and analysis of 55 patients with hemophilia A in Shandong Province [J]. Journal of Shandong University (Health Sciences), 2019, 57(12): 57-61.
[11] HU Liping, WANG Le, JIN Liang, LIU Yanxia, CUI Dongqing, CAO Lili. A case report and literature review of complex heterozygous SYNE1 mutation with autosomal recessive cerebellar ataxia type1 [J]. Journal of Shandong University (Health Sciences), 2019, 57(11): 78-82.
[12] XIAO Hongmei. Advance in genetic study on oocyte maturation failure [J]. Journal of Shandong University (Health Sciences), 2018, 56(4): 18-22.
[13] LU Min, CHEN Yun, DING Botong, CHANG Yali, ZHOU Yawei, ZHAO Aiping, GUO Nongjian. Gene detection and analysis for hemophilia B among populations in Shandong Province [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(3): 87-92.
[14] SUN Jin, HAN Bo, WEI Mei-li, YANG Wen-wei, WANG Jie-zhong, LIU Yong-jiao. Mutation screening of TFAP2B gene in children with patent ductus arteriosus [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(3): 72-75.
[15] SUN Ya-fang1, WANG Yin-chang2, WANG Lai-cheng3, JIAO Yu-lian3, CUI Bin3, XIA Yu3, LU Bing-ru3, ZHAO Yue-ran1,3. Mutation analysis of SQSTM1 and TNFRSF11A genes in
a Chinese family with Paget disease of bone [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(12): 107-113.
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