First description of an unusual novel double mutation in MECP2 co-occurring with the m.827A>G mutation in the MT-RNR1 gene associated with angelman-like syndrome.
AS-like
Double mutation
MECP2
Somatic mosaicism
mtDNA
Journal
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
ISSN: 1873-474X
Titre abrégé: Int J Dev Neurosci
Pays: United States
ID NLM: 8401784
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
26
06
2019
revised:
01
09
2019
accepted:
07
10
2019
pubmed:
28
10
2019
medline:
12
5
2020
entrez:
25
10
2019
Statut:
ppublish
Résumé
Mutations in Methyl-CpG-Binding protein 2 (MECP2), located on Xq28 and encoding a methyl CpG binding protein, are commonly related to Rett syndrome. However, MECP2 mutations have already been reported in patients with neurodevelopmental abnormalities such as X-linked mental retardation, severe neonatal encephalopathy and Angelman-like syndrome (AS-like). Accordingly, we report the clinical, molecular and bioinformatic analyses in a Tunisian patient with AS-like phenotype. In fact, the direct sequencing of MECP2 and cloning essay reveals the emergence of an unusual novel double mutation, including a de novo mutation c.397C > T (p.R133C) and an inherited one c.608C > T (p.T203 M) co-occurring in Trans. We also provide the molecular evidence of the c.608C > T transmission to the patient which was present in her father at somatic mosaicism state. To gain insight into the molecular basis of this disorder, we undertook, for the first time, a whole mitochondrial genome mutational analysis. Thus, the results showed the presence of several variations and a homoplasmic mutation m.827A > G in the MT-RNR1 gene, leading to the disruption of the 12S rRNA secondary structure. Our report is considered as the first to describe an unusual novel double mutation (c.397C > T in trans with c.608C > T) in MECP2 co-occurring with the mitochondrial m.827A > G mutation in the MT-RNR1 gene in a Tunisian patient with AS-like. Besides, our results highlight the importance of studying MECP2 and the significance of mDNA screening in AS-like disorder for a better understanding of its etiopathogenesis.
Identifiants
pubmed: 31647993
doi: 10.1016/j.ijdevneu.2019.10.002
doi:
Substances chimiques
MECP2 protein, human
0
Methyl-CpG-Binding Protein 2
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
37-44Informations de copyright
Copyright © 2019 ISDN. Published by Elsevier Ltd. All rights reserved.
Références
I.A. Adzhubei, S. Schmidt, L. Peshkin, V.E. Ramensky, A. Gerasimova, P. Bork, A.S. Kondrashov, S.R. Sunyaev. A method and server for predicting damaging missense mutations. Nat. Methods. 7: 2010; 248-249 10.1038/nmeth0410-248
R.C. Allen, H.Y. Zoghbi, A.B. Moseley, H.M. Rosenblatt, J.W. Belmont. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am. J. Hum. Genet. 51: 1992; 1229-1239
R.E. Amir, I.B. Van den Veyver, M. Wan, C.Q. Tran, U. Francke, H.Y. Zoghbi. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23: 1999; 185-188 10.1038/13810
A. Bebbington, A. Anderson, D. Ravine, S. Fyfe, M. Pineda, N. de Klerk, B. Ben-Zeev, N. Yatawara, A. Percy, W.E. Kaufmann, H. Leonard. Investigating genotype-phenotype relationships in Rett syndrome using an international data set. Neurology. 70: 2008; 868-875 10.1212/01.wnl.0000304752.50773.ec
J. Bendl, J. Stourac, O. Salanda, A. Pavelka, E.D. Wieben, J. Zendulka, J. Brezovsky, J. Damborsky. PredictSNP: robust and accurate consensus classifier for prediction of disease-related mutations. PLoS Comput. Biol. 10: 2014 e100344010.1371/journal.pcbi.1003440
L.M. Bird. Angelman syndrome: review of clinical and molecular aspects. Appl. Clin. Genet. 7: 2014; 93-104 10.2147/TACG.S57386
I.M. Buyse, P. Fang, K.T. Hoon, R.E. Amir, H.Y. Zoghbi, B.B. Roa. Diagnostic testing for rett syndrome by DHPLC and direct sequencing analysis of the MECP2 gene: identification of several novel mutations and polymorphisms. Am. J. Hum. Genet. 67: 2000; 1428-1436
F.J. Castora. Mitochondrial function and abnormalities implicated in the pathogenesis of ASD. Prog. Neuropsychopharmacol. Biol. Psychiatry. 92: 2019; 83-108 10.1016/j.pnpbp.2018.12.015
M.R. Chaig, M.E. Zernotti, N.W. Soria, O.F. Romero, M.F. Romero, N.M. Gerez. A mutation in mitochondrial 12S rRNA, A827G, in Argentinean family with hearing loss after aminoglycoside treatment. Biochem. Biophys. Res. Commun. 368: 2008; 631-636 10.1016/j.bbrc.2008.01.143
C.A. Chapleau, J. Lane, S.M. Kirwin, C. Schanen, K.M.B. Vinette, D. Stubbolo, P. MacLeod, A.K. Percy. Detection of rarely identified multiple mutations in MECP2 gene do not contribute to enhanced severity in rett syndrome. American journal of medical genetics. Part A. 161: 2013; 163810.1002/ajmg.a.35979
B.-O. Choi, J.H. Hwang, E.M. Cho, E.H. Jeong, Y.S. Hyun, H.J. Jeon, K.M. Seong, N.S. Cho, K.W. Chung. Mutational analysis of whole mitochondrial DNA in patients with MELAS and MERRF diseases. Exp. Mol. Med. 42: 2010; 446-455 10.3858/emm.2010.42.6.046
V.A. Cuddapah, R.B. Pillai, K.V. Shekar, J.B. Lane, K.J. Motil, S.A. Skinner, D.C. Tarquinio, D.G. Glaze, G. McGwin, W.E. Kaufmann, A.K. Percy, J.L. Neul, M.L. Olsen. Methyl-CpG-binding protein 2 (MEPC2) mutation type is associated with disease severity in Rett Syndrome. J. Med. Genet. 51: 2014; 152-158 10.1136/jmedgenet-2013-102113
C. Depienne, D. Bouteiller, B. Keren, E. Cheuret, K. Poirier, O. Trouillard, B. Benyahia, C. Quelin, W. Carpentier, S. Julia, A. Afenjar, A. Gautier, F. Rivier, S. Meyer, P. Berquin, M. Hélias, I. Py, S. Rivera, N. Bahi-Buisson, I. Gourfinkel-An, C. Cazeneuve, M. Ruberg, A. Brice, R. Nabbout, E. Leguern. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet. 5: 2009 e100038110.1371/journal.pgen.1000381
O. Eeg-Olofsson, A.G. al-Zuhair, A.S. Teebi, A.S. Daoud, M. Zaki, M.S. Besisso, M.M. Al-Essa. Rett syndrome: a mitochondrial disease?. J. Child Neurol. 5: 1990; 210-214 10.1177/088307389000500311
N. Fendri-Kriaa, Z. Abdelkafi, I.B. Rebeh, F. Kamoun, C. Triki, F. Fakhfakh. A novel MECP2 gene mutation in a Tunisian patient with Rett syndrome. Genet. Test. Mol. Biomarkers. 13: 2009; 109-113 10.1089/gtmb.2008.0076
W. Fu, T.D. O'Connor, G. Jun, H.M. Kang, G. Abecasis, S.M. Leal, S. Gabriel, M.J. Rieder, D. Altshuler, J. Shendure, D.A. Nickerson, M.J. Bamshad, NHLBI Exome Sequencing Project, J.M. Akey. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature. 493: 2013; 216-220 10.1038/nature11690
N. Geerdink, J.J. Rotteveel, M. Lammens, E.A. Sistermans, G.T. Heikens, F.J.M. Gabreëls, R.A. Mullaart, B.C.J. Hamel. MECP2 mutation in a boy with severe neonatal encephalopathy: clinical, neuropathological and molecular findings. Neuropediatrics. 33: 2002; 33-36 10.1055/s-2002-23598
W.A. Gold, R. Krishnarajy, C. Ellaway, J. Christodoulou. Rett syndrome: a genetic update and clinical review focusing on comorbidities. ACS Chem. Neurosci. 9: 2018; 167-176 10.1021/acschemneuro.7b00346
W. Gratzer. Human genetics. Silence speaks in spectrin. Nature. 372: 1994; 620-621 10.1038/372620a0
I.L. Hofacker. Vienna RNA secondary structure server. Nucleic Acids Res. 31: 2003; 3429-3431
M. Källberg, H. Wang, S. Wang, J. Peng, Z. Wang, H. Lu, J. Xu. Template-based protein structure modeling using the RaptorX web server. Nat. Protoc. 7: 2012; 1511-1522 10.1038/nprot.2012.085
M. Kharrat, Y. Kamoun, F. Kamoun, E. Ellouze, M. Maalej, N. Fendri-Kriaa, L. Ammar-Keskes, N. Belghith, A. Gargouri, C. Triki, F. Fakhfakh. Clinical, molecular, and computational analysis in patients with a novel double mutation and a new synonymous variant in MeCP2: report of the first missense mutation within the AT-hook1 cluster in rett syndrome. J. Child Neurol. 32: 2017; 694-703 10.1177/0883073817701622
A. Kochański. Pathogenic mutations and non-pathogenic DNA polymorphisms in the most common neurodegenerative disorders. Folia Neuropathol. 45: 2007; 164-169
M. Lek, K.J. Karczewski, E.V. Minikel, et al.Analysis of protein-coding genetic variation in 60,706 humans. Nature. 536: 2016; 28510.1038/nature19057
S.H. Lelieveld, J.A. Veltman, C. Gilissen. Novel bioinformatic developments for exome sequencing. Hum. Genet. 135: 2016; 603-614 10.1007/s00439-016-1658-6
I.U.S. Leong, A. Stuckey, D. Lai, J.R. Skinner, D.R. Love. Assessment of the predictive accuracy of five in silico prediction tools, alone or in combination, and two metaservers to classify long QT syndrome gene mutations. BMC Med. Genet. 16: 2015; 3410.1186/s12881-015-0176-z
H.A. Lewin, J.A. Stewart-Haynes. A simple method for DNA extraction from leukocytes for use in PCR. BioTechniques. 13: 1992; 522-524
M.T. Lott, J.N. Leipzig, O. Derbeneva, H.M. Xie, D. Chalkia, M. Sarmady, V. Procaccio, D.C. Wallace. mtDNA variation and analysis using MITOMAP and MITOMASTER. Curr. Protoc. Bioinformatics. 1: 2013; 1.23.1-1.23.26 10.1002/0471250953.bi0123s44
T.A. Manolio, F.S. Collins, N.J. Cox, D.B. Goldstein, L.A. Hindorff, D.J. Hunter, M.I. McCarthy, E.M. Ramos, L.R. Cardon, A. Chakravarti, J.H. Cho, A.E. Guttmacher, A. Kong, L. Kruglyak, E. Mardis, C.N. Rotimi, M. Slatkin, D. Valle, A.S. Whittemore, M. Boehnke, A.G. Clark, E.E. Eichler, G. Gibson, J.L. Haines, T.F.C. Mackay, S.A. McCarroll, P.M. Visscher. Finding the missing heritability of complex diseases. Nature. 461: 2009; 747-753 10.1038/nature08494
J.L. Neul, W.E. Kaufmann, D.G. Glaze, J. Christodoulou, A.J. Clarke, N. Bahi-Buisson, H. Leonard, M.E.S. Bailey, N.C. Schanen, M. Zappella, A. Renieri, P. Huppke, A.K. Percy. Rett syndrome: revised diagnostic criteria and nomenclature. Ann. Neurol. 68: 2010; 944-950 10.1002/ana.22124
P.C. Ng, S. Henikoff. Accounting for human polymorphisms predicted to affect protein function. Genome Res. 12: 2002; 436-446 10.1101/gr.212802
A. Orrico, C. Lam, L. Galli, M.T. Dotti, G. Hayek, S.F. Tong, P.M. Poon, M. Zappella, A. Federico, V. Sorrentino. MECP2 mutation in male patients with non-specific X-linked mental retardation. FEBS Lett. 481: 2000; 285-288
Y. Qi, Z. Liu, S. Jiang. [Five de novo forms of polymorphisms first found in Chinese mitochondrial genome]. Zhonghua Yi Xue Za Zhi. 81: 2001; 924-926
J.M. Schwarz, D.N. Cooper, M. Schuelke, D. Seelow. MutationTaster2: mutation prediction for the deep-sequencing age. Nat. Methods. 11: 2014; 361-362 10.1038/nmeth.2890
H.A. Shihab, J. Gough, D.N. Cooper, P.D. Stenson, G.L.A. Barker, K.J. Edwards, I.N.M. Day, T.R. Gaunt. Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum. Mutat. 34: 2013; 57-65 10.1002/humu.22225
N. Shulyakova, A.C. Andreazza, L.R. Mills, J.H. Eubanks. Mitochondrial dysfunction in the pathogenesis of rett syndrome: implications for mitochondria-targeted therapies. Front. Cell. Neurosci. 11: 2017 10.3389/fncel.2017.00058
H. Su, W. Fan, P.E. Coskun, J. Vesa, J.-A. Gold, Y.-H. Jiang, P. Potluri, V. Procaccio, A. Acab, J.H. Weiss, D.C. Wallace, V.E. Kimonis. Mitochondrial dysfunction in CA1 hippocampal neurons of the UBE3A deficient mouse model for Angelman syndrome. Neurosci. Lett. 487: 2011; 129-133 10.1016/j.neulet.2009.06.079
S.V. Tavtigian, A.M. Deffenbaugh, L. Yin, T. Judkins, T. Scholl, P.B. Samollow, D. de Silva, A. Zharkikh, A. Thomas. Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral. J. Med. Genet. 43: 2006; 295-305 10.1136/jmg.2005.033878
The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 526: 2015; 68-74 10.1038/nature15393
P. Watson, G. Black, S. Ramsden, M. Barrow, M. Super, B. Kerr, J. Clayton-Smith. Angelman syndrome phenotype associated with mutations in MECP2, a gene encoding a methyl CpG binding protein. J. Med. Genet. 38: 2001; 224-228 10.1136/jmg.38.4.224
L.S. Weaving, S.L. Williamson, B. Bennetts, M. Davis, C.J. Ellaway, H. Leonard, M.-K. Thong, M. Delatycki, E.M. Thompson, N. Laing, J. Christodoulou. Effects of MECP2 mutation type, location and X-inactivation in modulating Rett syndrome phenotype. Am. J. Med. Genet. A. 118A: 2003; 103-114 10.1002/ajmg.a.10053
Z. Wen, T.-L. Cheng, G. Li, S.-B. Sun, S.-Y. Yu, Y. Zhang, Y.-S. Du, Z. Qiu. Identification of autism-related MECP2 mutations by whole-exome sequencing and functional validation. Mol. Autism. 8: 2017 10.1186/s13229-017-0157-5
C.A. Williams, A.L. Beaudet, J. Clayton-Smith, J.H. Knoll, M. Kyllerman, L.A. Laan, R.E. Magenis, A. Moncla, A.A. Schinzel, J.A. Summers, J. Wagstaff. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am. J. Med. Genet. A. 140: 2006; 413-418 10.1002/ajmg.a.31074
G. Xing, Z. Chen, Q. Wei, H. Tian, X. Li, A. Zhou, X. Bu, X. Cao. Maternally inherited non-syndromic hearing loss associated with mitochondrial 12S rRNA A827G mutation in a Chinese family. Biochem. Biophys. Res. Commun. 344: 2006; 1253-1257 10.1016/j.bbrc.2006.04.033