A non-syndromic intellectual disability associated with a de novo microdeletion at 7q and 18p, microduplication at Xp, and 18q partial trisomy detected using chromosomal microarray analysis approach

Molecular Cytogenetics

Aparecido Divino da Cruz⁶  Daniela de Melo e Silva⁵  Claudio Carlos da Silva⁶  Cristiano Luiz Ribeiro³  Rodrigo Roncato Pereira²  Damiana Míriam da Cruz e Cunha⁴  Aldaires Vieira de Melo¹  Alex Silva da Cruz²  Lysa Bernardes Minasi⁴  Irene Plaza Pinto⁴ 

[1] Universidade Federal de Goiás, Programa de Pós Graduação em Biotecnologia e Biodiversidade, Rede Centro Oeste de Pós Graduação, Pesquisa e Inovação, Campus Samambaia, Goiânia, GO, Brazil;Universidade Federal de Goiás, Instituto de Ciências Biológicas, Programa de Pós Graduação em Biologia, Campus Samambaia, Goiânia, GO, Brazil;Departamento de Biologia, Pontifícia Universidade Católica de Goiás, Núcleo de Pesquisas Replicon, Rua 235, n. 40, Bloco L, Área IV Setor Universitário, Goiânia, GO, Brazil;Departamento de Biologia, Pontifícia Universidade Católica de Goiás, Mestrado em Genética, Programa de Pós Graduação Mestrado em Genética, Rua 235, n. 40, Bloco L, Área IV Setor Universitário, Goiânia, GO, Brazil;Programa de Pós-Graduação em Genética e Biologia Molecular, Laboratório de Genética e Biodiversidade, Universidade Federal de Goiás, Goiânia, GO, Brazil;Laboratório de Citogenética Humana e Genética Molecular, Secretaria do Estado da Saúde de Goiás (LACEN/SESGO), Goiânia, GO, Brazil

关键词: Mosaicism;    Microduplication;    Microdeletion;    18q partial trisomy;    CMA;    Intellectual disability;   

Others  :  1149990
DOI  :  10.1186/1755-8166-7-44

 received in 2014-03-10, accepted in 2014-06-20,  发布年份 2014

【 摘 要 】

Background

Chromosome abnormalities that segregate with a disease phenotype can facilitate the identification of disease loci and genes. The relationship between chromosome 18 anomalies with severe intellectual disability has attracted the attention of cytogeneticists worldwide. Duplications of the X chromosome can cause intellectual disability in females with variable phenotypic effects, due in part to variations in X-inactivation patterns. Additionally, deletions of the 7qter region are associated with a range of phenotypes.

Results

We report the first case of de novo microdeletion at 7q and 18p, 18q partial trisomy, microduplication at Xp associated to intellectual disability in a Brazilian child, presenting a normal karyotype. Karyotyping showed any chromosome alteration. Chromosomal microarray analysis detected a de novo microdeletion at 18p11.32 and 18q partial trisomy, an inherited microdeletion at 7q31.1 and a de novo microduplication at Xp22.33p21.3.

Conclusions

Our report illustrates a case that presents complex genomic imbalances which may contribute to a severe clinical phenotypes. The rare and complex phenotypes have to be investigated to define the subsets and allow the phenotypes classification.

【 授权许可】

   
2014 Pinto et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Cho AR, Kim HR, Lee MK, Yun SW, Lee JJ: Partial trisomy of chromosome 18q11.2-q12: a case report. Korean J Pedatr 2009, 52:1171-1174.
• [2]d’Orsi G, Pascarella MG, Pansini A, Buonadonna AL, Trivisano M, Pacillo F, Carapelle E, Demaio V, Minervini M, Gentile M, Specchio LM: Partial trisomy 18q and epileptic spasms induced by eating associated with bilateral opecular dysplasia. Am J Med Genet Part A 2013, 161A:1194-1195.
• [3]Iourov IY, Vorsanova SG, Yurov YB: Somatic genome variations in health and disease. Curr Genomics 2010, 11(6):387-96.
• [4]Holden ST, Clarkson A, Thomas NS, Abbott K, James MR, Willatt L: A de novo duplication of Xp11.22–p11.4 in a girl with intellectual disability, structural brain anomalies, and preferential inactivation of the normal X chromosome. Am J Med Gent Part A 2010, 152A:1735-1740.
• [5]Sheath KL, Mazzaschi RL, Aftimos S, Gregersen NE, George AM, Love DR: Clinical outcomes and counselling issues regarding partial trisomy of terminal Xp in a child with developmental delay. Sultan Qaboos Univ Med Jl 2013, 13(2):311-317.
• [6]Argiropoulos B, Carter M, Brierley K, Hare H, Bouchard A, Al-Hertani W, Ryan SR, Reid J, Basik M, McGowan-Jordan J, Graham GE: Discordant phenotypes in a mother and daughter with mosaic supernumerary ring chromosome 19 explained by a de novo 7q36.2 deletion and 7p22.1 duplication. Am J Med Genet A 2011, 155A(4):885-91.
• [7]Pelegrino Kde O, Sugayama S, Catelani AL, Lezirovitz K, Kok F, Chauffaille ML: 7q36 deletion and 9p22 duplication: effects of a double imbalance. Mol Cytogenet 2013, 6(1):2.
• [8]Elia J, Gai X, Xie HM, Perin JC, Geiger E, Glessner JT, D’arcy M, DeBerardinis R, Frackelton E, Kim C, Lantieri F, Muganga BM, Wang L, Takeda T, Rappaport EF, Grant SF, Berrettini W, Devoto M, Shaikh TH, Hakonarson H, White PS: Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol Psychiatry 2010, 15(6):637-46.
• [9]Maestrini E, Pagnamenta AT, Lamb JA, Bacchelli E, Sykes NH, Sousa I, Toma C, Barnby G, Butler H, Winchester L, Scerri TS, Minopoli F, Reichert J, Cai G, Buxbaum JD, Korvatska O, Schellenberg GD, Dawson G, de Bildt A, Minderaa RB, Mulder EJ, Morris AP, Bailey AJ, Monaco AP, IMGSAC: High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility. Mol Psychiatry 2010, 15:954-968.
• [10]Petek E, Windpassinger C, Vincent JB, Cheung J, Boright AP, Scherer SW, Kroisel PM, Wagner K: Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. Am J Hum Genet 2001, 68(4):848-58.
• [11]Freson K, Hashimoto H, Thys C, Wittevrongel C, Danloy S, Morita Y, Shintani N, Tomiyama Y, Vermylen J, Hoylaerts MF, Baba A, Van Geet C: The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation. J Clin Invest 2004, 113:905-912.
• [12]Turleau C: Monosomy 18p. Orphanet J Rare Dis 2008, 3:1-5.
• [13]Cereda A, Carey JC: The trisomy 18 syndrome. Orphanet J Rare Dis 2012, 7:81-94.
• [14]Fitas AL, Paiva M, Cordeiro AI, Nunes L, Cordeiro-Ferreira G: Mosaic trisomy 18 in a five-month-old infant. Case Rep Pediatr 2013, 2013(Article ID 929861):1-3.
• [15]Tucker ME, Garringer HJ, Weaver DD: Phenotypic spectrum of mosaic trisomy 18: two new patients, a literature review, and counseling issues. Am J Med Genet A 2007, 143(5):505-17.
• [16]Daoud H, Bonnet-Brilhault F, Védrine S, Demattéi MV, Vourc’h P, Bayou N, Andres CR, Barthélémy C, Laumonnier F, Briault S: Autism and nonsyndromic mental retardation associated with a de novo mutation in the NLGN4X gene promoter causing an increased expression level. Biol Psychiatry 2009, 66:906-910.
• [17]Tarpey PS, Stevens C, Teague J, Edkins S, O’Meara S, Avis T, Barthorpe S, Buck G, Butler A, Cole J, Dicks E, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, West S, Widaa S, Yates A, Catford R, et al.: Mutations in the gene encoding the sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation. Am J Hum Genet 2006, 79:1119-1124.
• [18]Chograni M, Rejeb I, Jemaa LB, Châabouni M, Bouhamed HC: The first missense mutation of NHS gene in a Tunisian family with clinical features of NHS syndrome including cardiac anomaly. Eur J Hum Genet 2011, 19:851-856.
• [19]Hagebeuk EE, van den Bossche RA, de Weerd AW: Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene. Dev Med Child Neurol 2013, 55:480-484.
• [20]Das DK, Mehta B, Menon SR, Raha S, Udani V: Novel Mutations in cyclin-dependent kinase-like 5 (CDKL5) gene in Indian cases of Rett Syndrome. Neuromol Med 2013, 15:218-225.
• [21]Tejada MI, Martínez-Bouzas C, García-Ribes A, Larrucea S, Acquadro F, Cigudosa JC, Belet S, Froyen G, López-Aríztegui MA: A child with mild X-linked intellectual disability and a microduplication at Xp22.12 including RPS6KA3. Pediatrics 2011, 128:1029-1033.
• [22]Matsumoto A, Kuwajima M, Miyake K, Kojima K, Nakashima N, Jimbo EF, Kubota T, Momoi MY, Yamagata T: An Xp22.12 microduplication including RPS6KA3 identified in a family with variably affected intellectual and behavioral disabilities. J Hum Genet 2013, 58:755-757.
• [23]Bornholdt D, Atkinson TP, Bouadjar B, Catteau B, Cox H, De Silva D, Fischer J, Gunasekera CN, Hadj-Rabia S, Happle R, Holder-Espinasse M, Kaminski E, König A, Mégarbané A, Mégarbané H, Neidel U, Oeffner F, Oji V, Theos A, Traupe H, Vahlquist A, van Bon BW, Virtanen M, Grzeschik KH: Genotype–Phenotype correlations emerging from the identification of missense mutations in MBTPS2. Hum Mutat 2013, 34(4):587-594.
• [24]Verma RS, Babu A: Human chromosomes: Principles and Techiniques. New York: MacGraw-Hill; 1995.
• [25]Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, et al.: Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010, 86(5):749-764.
• [26]Battaglia A, Doccini V, Bernardini L, Novelli A, Loddo S, Capalbo A, Filippi T, Carey JC: Confirmation of chromosomal microarray as a first-tier clinical diagnostic test for individuals with developmental delay, intellectual disability, autism spectrum disorders and dysmorphic features. Eur J Paediatr Neurol 2013, 17(6):589-99.