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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2017

Open Access 01-12-2017 | Research article

Clinical and molecular genetic characterization of familial MECP2 duplication syndrome in a Chinese family

Authors: Xiaoyan Li, Hua Xie, Qian Chen, Xiongying Yu, Zhaoshi Yi, Erzhen Li, Ting Zhang, Jian Wang, Jianmin Zhong, Xiaoli Chen

Published in: BMC Medical Genetics | Issue 1/2017

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Abstract

Background

Chromosomal duplication at the Xq28 region including the MECP2 gene, share consistent clinical phenotypes and a distinct facial phenotype known as MECP2 duplication syndrome. The typical clinical features include infantile hypotonia, mild dysmorphic features, a broad range of neurodevelopmental disorders, recurrent infections, and progressive spasticity.

Methods

This Chinese MECP2 duplication syndrome family includes six patients (five males and one female), and four asymptomatic female carriers. Two kinds of chips including 4x180K CNV + SNP chip and custom 8x60K CNV chip were used to detect MECP2 duplication, and then fluorescent in situ hybridization (FISH) analysis was performed to identify the exact copy number of MECP2. X-chromosome inactivation (XCI) analysis on AR gene was detected for all female family members, and the microsatellite analysis on MECP2 was used to validate the recombination event on MECP2 region.

Results

The affected male subjects presented with a broad range of neurodevelopmental symptoms (severe intellectual disability, developmental delay, seizure, language deficit, and autism spectrum disorder) as well as facial dysmorphism and other symptoms which were consistent with that of Western patients previous reported. Seizure is reported in Chinese patients for the first time. In addition, we validated three recombination events for the MECP2-duplication allele during maternal transmission due to X homologous recombination.

Conclusions

We provided the largest known Chinese pedigree with MECP2 duplication syndrome. The detailed clinical description and molecular genetic characterization in all affected family members further delineate the typical phenotype of this genomic disorder in Chinese population.
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Literature
1.
Bassani S, Zapata J, Gerosa L, Moretto E, Murru L, Passafaro M. The neurobiology of X-linked intellectual disability. The Neuroscientist. 2013;19(5):541–52.CrossRefPubMed
2.
Gecz J, Shoubridge C, Corbett M. The genetic landscape of intellectual disability arising from chromosome X. Trends Genet. 2009;25(7):308–16.CrossRefPubMed
3.
Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2):185–8.CrossRefPubMed
4.
Meins M, Lehmann J, Gerresheim F, Herchenbach J, Hagedorn M, Hameister K, et al. Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome. J Med Genet. 2005;42(2):e12.CrossRefPubMedPubMedCentral
5.
Bauer M, Kolsch U, Kruger R, Unterwalder N, Hameister K, Kaiser FM, et al. Infectious and immunologic phenotype of MECP2 duplication syndrome. J Clin Immunol. 2015;35(2):168–81.CrossRefPubMed
6.
7.
Xu X, Xu Q, Zhang Y, Zhang X, Cheng T, Wu B, et al. A case report of Chinese brothers with inherited MECP2-containing duplication: autism and intellectual disability, but not seizures or respiratory infections. BMC Med Genet. 2012;13:75.CrossRefPubMedPubMedCentral
8.
Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet. 2005;77(3):442–53.CrossRefPubMedPubMedCentral
9.
Honda S, Satomura S, Hayashi S, Imoto I, Nakagawa E, Goto Y, et al. Concomitant microduplications of MECP2 and ATRX in male patients with severe mental retardation. J Hum Genet. 2012;57(1):73–7.CrossRefPubMed
10.
Hanchard NA, Carvalho CM, Bader P, Thome A, Omo-Griffith L, del Gaudio D, et al. A partial MECP2 duplication in a mildly affected adult male: a putative role for the 3′ untranslated region in the MECP2 duplication phenotype. BMC Med Genet. 2012;13:71.CrossRefPubMedPubMedCentral
11.
Van Esch H. MECP2 duplication syndrome. Mol Syndromology. 2012;2(3–5):128–36.
12.
Shimada S, Okamoto N, Ito M, Arai Y, Momosaki K, Togawa M, et al. MECP2 duplication syndrome in both genders. Brain Dev. 2013;35(5):411–9.CrossRefPubMed
13.
14.
Shimada S, Okamoto N, Hirasawa K, Yoshii K, Tani Y, Sugawara M, et al. Clinical manifestations of Xq28 functional disomy involving MECP2 in one female and two male patients. Am J Med Genet A. 2013;161A(7):1779–85.CrossRefPubMed
15.
Vignoli A, Borgatti R, Peron A, Zucca C, Ballarati L, Bonaglia C, et al. Electroclinical pattern in MECP2 duplication syndrome: eight new reported cases and review of literature. Epilepsia. 2012;53(7):1146–55.CrossRefPubMed
16.
Trobaugh-Lotrario A, Martin J, Lopez-Terrada D. Hepatoblastoma in a male with MECP2 duplication syndrome. Am J Med Genet A. 2016;170(3):790–1.CrossRefPubMed
17.
Caumes R, Boespflug-Tanguy O, Villeneuve N, Lambert L, Delanoe C, Leheup B, et al. Late onset epileptic spasms is frequent in MECP2 gene duplication: electroclinical features and long-term follow-up of 8 epilepsy patients. Eur J Paediatr Neurol. 2014;18(4):475–81.CrossRefPubMed
18.
Tang SS, Fernandez D, Lazarou LP, Singh R, Fallon P. MECP2 triplication in 3 brothers - a rarely described cause of familial neurological regression in boys. Eur J Paediatr. 2012;16(2):209–12.CrossRef
19.
Fernandez RM, Nunez-Torres R, Gonzalez-Meneses A, Antinolo G, Borrego S. Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region. BMC Med Genet. 2010;11:137.CrossRefPubMedPubMedCentral
20.
Peters SU, Hundley RJ, Wilson AK, Warren Z, Vehorn A, Carvalho CM, et al. The behavioral phenotype in MECP2 duplication syndrome: a comparison with idiopathic autism. Autism Res. 2013;6(1):42–50.CrossRefPubMed
21.
Fukushi D, Yamada K, Nomura N, Naiki M, Kimura R, Yamada Y, et al. Clinical characterization and identification of duplication breakpoints in a Japanese family with Xq28 duplication syndrome including MECP2. Am J Med Genet A. 2014;164A(4):924–33.CrossRefPubMed
22.
Lin DS, Chuang TP, Chiang MF, Ho CS, Hsiao CD, Huang YW, et al. De novo MECP2 duplication derived from paternal germ line result in dysmorphism and developmental delay. Gene. 2014;533(1):78–85.CrossRefPubMed
23.
Neira VA, Romero-Espinoza P, Rojas-Martinez A, Ortiz-Lopez R, Cordova-Fletes C, Plaja A, et al. De novo MECP2 disomy in a Mexican male carrying a supernumerary marker chromosome and no typical Lubs syndrome features. Gene. 2013;524(2):381–5.CrossRefPubMed
24.
de Palma L, Boniver C, Cassina M, Toldo I, Nosadini M, Clementi M, et al. Eating-induced epileptic spasms in a boy with MECP2 duplication syndrome: insights into pathogenesis of genetic epilepsies. Epileptic Disord. 2012;14(4):414–7.PubMed
25.
Xu Q, Goldstein J, Wang P, Gadi IK, Labreche H, Rehder C, et al. Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge. Pediatr Res. 2016;80(3):371–81.CrossRefPubMedPubMedCentral
26.
Chen XL, Guo J, Wang J, Wang LW, Ding XY, Zhang T, et al. Genomic copy number variations in children with unexplained mental retardation and developmental delay detected by array-comparative genomic hybridization. Chinese journal of evidence-based. Pediatrics. 2010;5(2):85–93.
27.
Yuan H, Zhu J, Deng X, Chen M, Li X, Li Q, et al. Chromosomal microarray analysis of 2000 pediatric cases. Chinese. J Med Genet. 2016;33(2):247–51.
28.
Shen Y, BL W. Microarray-based genomic DNA profiling technologies in clinical molecular diagnostics. Clin Chem. 2009;55(4):659–69.CrossRefPubMed
29.
Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW. 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. 1992;51(6):1229–39.PubMedPubMedCentral
30.
Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 1998;19(2):187–91.CrossRefPubMed
31.
Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998;393(6683):386–9.CrossRefPubMed
32.
Pai GS, Hane B, Joseph M, Nelson R, Hammond LS, Arena JF, et al. A new X linked recessive syndrome of mental retardation and mild dysmorphism maps to Xq28. J Med Genet. 1997;34(7):529–34.CrossRefPubMedPubMedCentral
33.
34.
del Gaudio D, Fang P, Scaglia F, Ward PA, Craigen WJ, Glaze DG, et al. Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males. Genet Med. 2006;8(12):784–92.CrossRefPubMed
35.
Fieremans N, Bauters M, Belet S, Verbeeck J, Jansen AC, Seneca S, et al. De novo MECP2 duplications in two females with intellectual disability and unfavorable complete skewed X-inactivation. Hum Genet. 2014;133(11):1359–67.CrossRefPubMed
36.
Auber B, Burfeind P, Thiels C, Alsat EA, Shoukier M, Liehr T, et al. An unbalanced translocation resulting in a duplication of Xq28 causes a Rett syndrome-like phenotype in a female patient. Clin Genet. 2010;77(6):593–7.CrossRefPubMed
37.
Sanlaville D, Prieur M, de Blois MC, Genevieve D, Lapierre JM, Ozilou C, et al. Functional disomy of the Xq28 chromosome region. Eur J Hum Genet. 2005;13(5):579–85.CrossRefPubMed
38.
Scott Schwoerer J, Laffin J, Haun J, Raca G, Friez MJ, Giampietro PF. MECP2 duplication: possible cause of severe phenotype in females. Am J Med Genet A. 2014;164A(4):1029–34.CrossRefPubMed
39.
Louise S, Fyfe S, Bebbington A, Bahi-Buisson N, Anderson A, Pineda M, et al. InterRett, a model for international data collection in a rare genetic disorder. Res Autism Spectr Disord. 2009;3(3)
Metadata
Title
Clinical and molecular genetic characterization of familial MECP2 duplication syndrome in a Chinese family
Authors
Xiaoyan Li
Hua Xie
Qian Chen
Xiongying Yu
Zhaoshi Yi
Erzhen Li
Ting Zhang
Jian Wang
Jianmin Zhong
Xiaoli Chen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-017-0486-4

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