Smith‑Magenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency

Zhou,Yi; Xie,Yingjun; Zhu,Yunxiao; Wu,Jianzhu; Shang,Meijiao; Chen,Baojiang; Fang,Qun

doi:10.3892/mmr.2015.4538

Smith‑Magenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency

Authors:
- Yi Zhou
- Yingjun Xie
- Yunxiao Zhu
- Jianzhu Wu
- Meijiao Shang
- Baojiang Chen
- Qun Fang
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Affiliations: Department of Obstetrics and Gynaecology, Fetal Medicine Center, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Ultrasonic Medicine, Fetal Medicine Center, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: November 9, 2015 https://doi.org/10.3892/mmr.2015.4538
Pages: 347-352

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Abstract

Smith‑Magenis syndrome (SMS) is a rare condition with multiple congenital malformations caused by the haploinsufficiency of RAI1 (deletion or mutation of RAI1). However, the correlation between genotype and phenotype is not well understood. The present study describes the prenatal diagnosis of monozygotic twins with a 17p11.2 deletion, which is indicative of SMS, who presented with discordant phenotypes and uteroplacental insufficiency. A high‑resolution genome‑wide single nucleotide polymorphism array revealed a 3.7‑Mb deletion in the 17p11.2 chromosome region. Accurate breakpoints of the deletion in these patients were used to identify correlations between SMS and the concomitant phenotypes, particularly uteroplacental insufficiency, which has rarely been investigated in SMS. In addition, no exonic mutations were identified in or affected known disease‑associated loci that could explain the congenital anomalies, according to a model that accounts for the possibility of incomplete penetrance. Furthermore, a novel benign copy number variation (a duplication of 195 kb at 13q12.13) was identified but was unlikely to be clinically significant in the discordant phenotypes of the twins. The present study showed that multiple interacting genetic and environmental factors are involved in determining the variance of the SMS phenotype.

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1	Smith ACM, Boyd KE, Elsea SH, et al: Smith-Magenis syndrome. Genereviews. Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT and Stephens K: Seattle (WA): 1993
2	Madduri N, Peters SU, Voigt RG, Llorente AM, Lupski JR and Potocki L: Cognitive and adaptive behavior profiles in Smith-Magenis syndrome. J Dev Behav Pediatr. 27:188–192. 2006. View Article : Google Scholar : PubMed/NCBI
3	Andrieux J, Villenet C, Quief S, Lignon S, Geffroy S, Roumier C, de Leersnyder H, de Blois MC, Manouvrier S, Delobel B, et al: Genotype phenotype correlation of 30 patients with Smith-Magenis syndrome (SMS) using comparative genome hybridisation array: Cleft palate in SMS is associated with larger deletions. J Med Genet. 44:537–540. 2007. View Article : Google Scholar : PubMed/NCBI
4	Gamba BF, Vieira GH, Souza DH, Monteiro FF, Lorenzini JJ, Carvalho DR and Morreti-Ferreira D: Smith-Magenis syndrome: Clinical evaluation in seven Brazilian patients. Genet Mol Res. 10:2664–2670. 2011. View Article : Google Scholar : PubMed/NCBI
5	De Leersnyder H: Smith-Magenis syndrome. Handb Clin Neurol. 111:295–296. 2013. View Article : Google Scholar : PubMed/NCBI
6	Hall JG: Twinning. Lancet. 362:735–743. 2003. View Article : Google Scholar : PubMed/NCBI
7	Girirajan S, Vlangos CN, Szomju BB, Edelman E, Trevors CD, Dupuis L, Nezarati M, Bunyan DJ and Elsea SH: Genotype-phenotype correlation in Smith-Magenis syndrome: Evidence that multiple genes in 17p11.2 contribute to the clinical spectrum. Genet Med. 8:417–427. 2006. View Article : Google Scholar : PubMed/NCBI
8	Singh SM, Murphy B and O'Reilly R: Monozygotic twins with chromosome 22q11 deletion and discordant phenotypes: Updates with an epigenetic hypothesis. J Med Genet. 39:e712002. View Article : Google Scholar : PubMed/NCBI
9	Desmaze C, Scambler P, Prieur M, Halford S, Sidi D, Le Deist F and Aurias A: Routine diagnosis of DiGeorge syndrome by fluorescent in situ hybridization. Hum Genet. 90:663–665. 1993. View Article : Google Scholar : PubMed/NCBI
10	Van Hemel JO, Schaap C, Van Opstal D, Mulder MP, Niermeijer MF and Meijers JH: Recurrence of DiGeorge syndrome: Prenatal detection by FISH of a molecular 22q11 deletion. J Med Genet. 32:657–658. 1995. View Article : Google Scholar : PubMed/NCBI
11	Hicks M, Ferguson S, Bernier F and Lemay JF: A case report of monozygotic twins with Smith-Magenis syndrome. J Dev Behav Pediatr. 29:42–46. 2008. View Article : Google Scholar : PubMed/NCBI
12	Halder A, Jain M, Chaudhary I and Varma B: Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype and deletion size. Mol Cytogenet. 5:132012. View Article : Google Scholar : PubMed/NCBI
13	Fahiminiya S, Almuriekhi M, Nawaz Z, Staffa A, Lepage P, Ali R, Hashim L, Schwartzentruber J, Abu Khadija K, Zaineddin S, et al: Whole exome sequencing unravels disease-causing genes in consanguineous families in Qatar. Clin Genet. 86:134–141. 2014. View Article : Google Scholar
14	Kono M, Sugiura K, Suganuma M, Hayashi M, Takama H, Suzuki T, Matsunaga K, Tomita Y and Akiyama M: Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of Kitamura, a clinical entity distinct from Dowling-Degos disease. Hum Mol Genet. 22:3524–3533. 2013. View Article : Google Scholar : PubMed/NCBI
15	Nuytemans K, Bademci G, Inchausti V, Dressen A, Kinnamon DD, Mehta A, Wang L, Züchner S, Beecham GW, Martin ER, et al: Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease. Neurology. 80:982–989. 2013. View Article : Google Scholar : PubMed/NCBI
16	Ravenscroft G, Thompson EM, Todd EJ, Yau KS, Kresoje N, Sivadorai P, Friend K, Riley K, Manton ND, Blumbergs P, et al: Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations. Neuromuscul Disord. 23:165–169. 2013. View Article : Google Scholar
17	Solomon BD, Hadley DW, Pineda-Alvarez DE, Kamat A, Teer JK, Cherukuri PF, Hansen NF, Cruz P, Young AC, Berkman BE, et al NISC Comparative Sequencing Program: Incidental medical information in whole-exome sequencing. Pediatrics. 129:e1605–e1611. 2012. View Article : Google Scholar : PubMed/NCBI
18	Verma R and Babu A: Human Chromosomes: Principles & Techniques. 2nd edition. McGraw-Hill; New York, NY: pp. 4191995, book review. Mol Reprod Devel. 43:1341996.
19	Gnirke A, Melnikov A, Maguire J, Rogov P, LeProust EM, Brockman W, Fennell T, Giannoukos G, Fisher S, Russ C, et al: Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat Biotechnol. 27:182–189. 2009. View Article : Google Scholar : PubMed/NCBI
20	Carmona-Mora P, Canales CP, Cao L, Perez IC, Srivastava AK, Young JI and Walz K: RAI1 transcription factor activity is impaired in mutants associated with Smith-Magenis Syndrome. PLoS One. 7:e451552012. View Article : Google Scholar : PubMed/NCBI
21	Lacaria M, Gu W and Lupski JR: Circadian abnormalities in mouse models of Smith-Magenis syndrome: Evidence for involvement of RAI1. Am J Med Genet A. 161A:1561–1568. 2013. View Article : Google Scholar : PubMed/NCBI
22	Girirajan S, Elsas LJ II, Devriendt K and Elsea SH: RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions. J Med Genet. 42:820–828. 2005. View Article : Google Scholar : PubMed/NCBI
23	Hayashi M, Kim SW, Imanaka-Yoshida K, Yoshida T, Abel ED, Eliceiri B, Yang Y, Ulevitch RJ and Lee JD: Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure. J Clin Invest. 113:1138–1148. 2004. View Article : Google Scholar : PubMed/NCBI
24	Burke C, Sinclair K, Cowin G, Rose S, Pat B, Gobe G and Colditz P: Intrauterine growth restriction due to uteroplacental vascular insufficiency leads to increased hypoxia-induced cerebral apoptosis in newborn piglets. Brain Res. 1098:19–25. 2006. View Article : Google Scholar : PubMed/NCBI
25	Uerpairojkit B, Manotaya S, Tanawattanacharoen S, Wuttikon sammakit P and Charoenvidhya D: Are the cardiac dimensions spared in growth-restricted fetuses resulting from uteroplacental insufficiency? J Obstet Gynaecol Res. 38:390–395. 2012. View Article : Google Scholar : PubMed/NCBI
26	Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino S, et al: CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature. 455:547–551. 2008. View Article : Google Scholar : PubMed/NCBI
27	Greene DM, Bloomfield G, Skelton J, Ivens A and Pears CJ: Targets downstream of Cdk8 in Dictyostelium development. BMC Dev Biol. 11:22011. View Article : Google Scholar : PubMed/NCBI
28	Huang N, Lee I, Marcotte EM and Hurles ME: Characterising and predicting haploinsufficiency in the human genome. PLoS Genet. 6:e10011542010. View Article : Google Scholar : PubMed/NCBI
29	Grayton HM, Fernandes C, Rujescu D and Collier DA: Copy number variations in neurodevelopmental disorders. Prog Neurobiol. 99:81–91. 2012. View Article : Google Scholar : PubMed/NCBI
30	Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, et al: A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med. 365:611–619. 2011. View Article : Google Scholar : PubMed/NCBI