MUTASYONDAN KLİNİĞE RETT SENDROMU

Yıl 2006, Cilt: 69 Sayı: 4, 120 - 125, 15.11.2011

Elif Yosunkaya Fenerci Adnan Yüksel Sebati Özdemir

Öz

Rett sendromu ilerleyici seyir gösteren, genetik temeli olan nörolojik bir hastalıktır. X’e bağlı dominant kalıtım modeline sahip olan hastalık çoğunlukla kız çocuklarda ortaya çıkmaktadır. Kızlarda gözlenen mental retardasyon nedenleri arasında Down sendromundan sonra ikinci sırada geldiği kabul edilmektedir. Genellikle doğum ve sonrasındaki 6-18. aylık süreçte normal gelişim gösteren çocuklarda hastalık zamanla gelişen mikrosefali, psikomotor gerilik ve amaçsız el hareketleriyle kendini gösterir. Sendromda otistik bulgulara sıkça rastlanılması bu sendromu birçok hastalığın ayırıcı tanısında daha çok gündeme getirmeye başlamıştır. Bu derleme Rett sendromunun moleküler temelindeki son gelişmelerden yola çıkarak etyolojiyle klinik tablo arasındaki ilişkiyi değerlendirmek amacıyla ele alınmıştır.

Anahtar Kelimeler

Rett sendromu, MECP2, CDKL5, X-dominant

Kaynakça

• Aber KM, Nori P, MacDonald SM, Bibat G, Jarrar MH, Ka- ufmann WE. Methyl-CpG-binding protein 2 is localized in the postsynaptic compartment: an immunochemical study of subcellular fractions. Neurosci 2003;116:77-80.
• Amir RE, Sutton VR, Van den Veyver IB. Newborn scre- ening and prenatal diagnosis for Rett syndrome: implications for therapy. J Child Neurol 2005;20:779-783
• Ariani F, Mari F, Pescucci C, Longo I, Bruttini M, Meloni I, Hayek G, Rocchi R, Zappella M, Renieri A. Real time quan- titative PCR as a routine method for screening large rearran- gements in Rett syndrome: Report of one case of MECP2 deletion and one case of MECP2 duplication. Human Mut 2004; 24:172-177.
• Bienvenu T, Chelly J. Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized. Nat Rev Genet 2006;7:415-426.
• Buyse IM, Fang P, Hoon KT, Amir RE, Zoghbi HY, Roa BB. Diagnostic testing for Rett syndrome by DHPLC and direct sequencing analysis of the MECP2 gene:identification of se- veral novel mutations and polymorphisms. Am J Hum Ge- net 2000; 67:1428-1436.
• Charman T, Neilson TC, Mash V, Archer H, Gardiner MT, Knudsen GP, McDonnell A, Perry J, Whatley SD, Bunyan DJ, Ravn K, Mount RH, Hastings RP, Hulten M, Orstavik KH, Reilly S, Cass H, Clarke A, Kerr AM, Bailey ME. Di- mensional phenotypic analysis and functional categorisation of mutations reveal novel genotype-phenotype associations in Rett syndrome. Eur J Hum Genet 2005; 13:1121-1130.
• De Bona C, Zappella M, Hayek G, Meloni I, Vitelli F, Brut- tini M, Cusano R, Loffredo P, Longo I, Renieri A. Preserved speech variant is allelic of classic Rett syndrome. Eur J Hum Genet 2000; 8:325-330.
• Egger J, Hofacker N, Schiel W, Holthausen H. Magnesium for hyperventilation in Rett`s syndrome. Lancet 1992;340:621-622.
• Ellaway C, Williams K, Leonard H, Higgins G, Wilcken B, Christodoulou J. Rett syndrome:randomized controlled trial of L-carnitine. J Child Neurol 1999; 14:162-167.
• Erlandson A, Samuelson L, Hagberg B, Kyllerman M, Vu- jic M, Wahlstrom J. Multiplex ligation-dependent probe amplification (MLPA) detects large deletions in the MECP2 gene of Swedish Rett syndrome patients. Genet Test 2003;7:329-332.
• Gill, H, Cheadle JP, Maynard J, Fleming N, Whatley S,Cranston T, Thompson EM, Leonard H, Davis M, Christo- doulou J, Skieldal O, Hanefeld F, Kerr A, Tandy A, Ravine D, Clarke A. Mutation analysis in the MECP2 gene and ge- netic counselling for Rett syndrome. J Med Genet 2003;40:380-384.
• Hagberg B, Hanefeld F, Percy A, Skjeldal O. An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett syndrome Clinical Criteria Consensus Panel Satellite to European Paediatric Neurology Society Meeting, Baden Baden, Germany, 11 September 2001. Eur J Peadiatr Neurol 2002;6:293-297.
• Heilstedt HA, Shahbazian MD, Lee B. Infantile hypotonia as a presentation of Rett syndrome. Am J Med Genet 2002;111:238-242.
• Kriaucionis S, Bird A.The major form of MECP2 has a no- vel N-terminus generated by alternative splicing. Nucl Acid Res 2004; 32:1818-1823.
• Laccone F, Junemann I, Whatley S, Morgan R, Butler R, Huppke P, Ravine D. Large deletions of the MECP2 gene de- tected by gene dosage analysis in patients with Rett syndro- me. Hum Mut 2004;23:234-244. Erratum appears in Hum Mut 2004; 23:395.
• Leonard H, Bower C, English D. The prevalence and inci- dence of Rett syndrome in Australia. Eur Child Adolesc Psych 1997; 1:8-10.
• Makedonski K, Abuhatzira L, Kaufman Y, Razin A, Shemer Y. MECP2 defiency in Rett syndrome causes epigenetic aberrations at the PWS/AS imprinting center that affects UBE3A expression. Hum Mol Genet 2005;14:1049-1058.
• Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Ca- selli R, Scala E, Longo I, Grosso S, Pescucci C, Ariani F, Ha- yek G, Balestri P, Bergo A, Badaracco G, Zappella M, Broc- coli V, Renieri A, Kilstrup-Nielsen C, Landsberger N. CDKL5 belongs to the same molecular pathway of MECP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet 2005; 15:14:1935-1946.
• McArthur AJ, Budden SS. Sleep dysfunction in Rett syndro- me: a trial of exogenous melatonin treatment. Dev Med Child Neurol 1998; 40:186-192.
• NomuraY, Segawa M. Natural history of Rett syndrome. J Child Neurol 2005; 764-768.
• Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MD. MIM Number: 176920: Proteus syndrome. http://www. ncbi.nlm.nih.gov.
• Ravn K, Nielsen JB, Schwartz M. Mutations found within exon 1 of MECP2 in Danish patients with Rett syndrome. (Letter) Clin Genet 2005;67:532-533.
• Samaco RC, Hogart A, LaSalle JM. Epigenetic overlap in autism-spectrum neurodevelopmental disorders:MECP2 de- ficiency causes reduced expression of UBE3A and GABRB3.Hum Mol Genet 2005;14:483-492.
• Scala E, Ariani F, Mari F, Caselli R, Pescucci C, Longo I, Meloni I, Giachino D, Bruttini M, Hayek G, Zappella M, Re- nieri A. CDKL5/STK9 is mutated in Rett syndrome variant with infantile spasms. J Med Genet 2005;42:103-107.
• Schanen C, Houwink EJ, Darrani N, Lane J, Everett R, Feng A, Cantor RM, Percy A. Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. Am J Med Genet 2004; 126:129-140.
• Schwartzman JS, Bernardino A, Nishimura A, Gomes RR, Zatz M. Rett syndrome in a boy with a 47,XXY karyotype confirmed by a rare mutation in the MECP2 gene. Neuropa- ediatr 2001;32:162-164.
• Smeets E, Terhal P, Casaer P, Peters A, Midro A, Schollen E, van Roozendaal K, Moog U, Matthiis G, Herbergs J, Smeets H, Curfs L, Schrander-Stumpel C, Fryns JP. Rett syndrome in females with CTS hot spot deletions: a disorder profile. Am J Med Genet 2005;132: 117-120.
• Stancheva I, Collins AL, Van den Veyver IB, Zoghbi H, Me- ehan RR. A mutant form of MECP2 protein associated with human Rett syndrome cannot be displaced from methylated DNA by notch in Xenopous embryos. Mol Cell 2003;12:425-435.
• Tao J, Van Esch H, Hagedorn-Greiwe M, Hoffmann K, Mo- ser B, Raynaud M, Sperner J, Fryns JP, Schwinger E, Gecz J, Ropers HH, Kalscheuer VM. Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are as- sociated with severe neurodevelopmental retardation. Am J Hum Genet 2004,75:1149-1154.
• Topcu M, Akyerli C, Sayi A, Toruner GA, Kocoglu SR, Cim- bis M, Özcelik T. Somatic mosaicism for a MECP2 mutati- on associated with classic Rett syndrome in a boy. Eur J Hum Genet 2002; 10:77-81.
• Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, Lugtenberg D, Bienvenu T, Jensen LR, Gecz J, Moraine C, Marynen P, Fryns JP, Froyen G. Duplication of the MECP2 region is a frequent cause of severe mental re- tardation and progressive neurological symptoms in males. Am J Hum Genet 2005;77:442-453.
• Weaving LS, Christodoulou J, Williamson SL, Friend KL, McKenzie OL, Archer H, Evans J, Clarke A, Pelka GJ, Tam PP, Watson C, Lahooti H, Ellaway CJ, Bennetts B, Leonard H, Gecz J. Mutations of CDKL5 cause a severe neurodeve- lopmental disorder with infantile spasms and mental retarda- tion. Am J Hum Genet 2004; 75: 1079-1093.
• Witt-Engerstrom I. Age-related occurrence of signs and symptoms in the Rett syndrome. Brain Dev 1992;14:11-20
• Young JI, Zoghbi HY. X-chromosome inactivation patterns are unbalanced and affect the phenotypic outcome in a mo- use model of Rett syndrome. Am J Hum Genet 2004;74:511- 550.
• Zlatanova J. MECP2:the chromatin connection and beyond. Biochem Cell Biol 2005; 83:251-262
• Zoghbi HY. Rett syndrome. GeneReviews, University of Washington, Seattle, 2004; http://www. genetests.com.