Abstract
Rett syndrome is a severe neurodevelopmental disorder that arises from mutations in the X-linked MECP2 gene. It is almost exclusively seen in girls due to the predominant occurrence of the mutations on the paternal X-chromosome, and also the early postnatal lethal effect of the disease causing mutations in hemizygous boys. We identified a boy with features of classic Rett syndrome who is mosaic for the truncating MECP2 mutation R270X. Chromosome analysis showed normal karyotype. These results indicate that a MECP2 mutation associated with Rett syndrome in females could lead to a similar phenotype in males as a result of somatic mosaicism.
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References
Rett A . Uber ein eigenartiges hirnatrophisches Syndrom bei Hyperammonemie im Kindesalter Wien Med Wochenschr 1966 116: 723–738
Hagberg B, Aicardi J, Dias K, Ramos O . A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases Ann Neurol 1983 14: 471–479
Schanen NC, Francke U . A severely affected male born into a Rett syndrome kindred supports X-linked inheritance and allows extension of the exclusion map Am J Hum Genet 1998 63: 267–269
Amir RE, Van den Veyver IB, Wan M et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 Nat Genet 1999 23: 185–188
Trevathan E, Naidu S . The clinical recognition and differential diagnosis of Rett syndrome J Child Neurol 1988 3 Suppl: S6–S16
Wan M, Sung Jae Lee S, Zhang X et al. Rett Syndrome and Beyond: Recurrent Spontaneous and Familial MECP2 Mutations at CpG Hotspots Am J Hum Genet 1999 65: 1520–1529
Meloni I, Bruttini M, Longo I et al. A mutation in the Rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males Am J Hum Genet 2000 67: 982–985
Clayton-Smith J, Watson P, Ramsden S, Black GCM . Somatic mutation in MECP2 as a non-fatal neurodevelopmental disorder in males Lancet 2000 356: 830–832
Watson P, Black G, Ramsden S et al. Angelman syndrome phenotype associated with mutations in MECP2, a gene encoding a methyl CpG binding protein J Med Genet 2001 38: 224–228
Philippart M . The Rett syndrome in males Brain Dev 1990 12: 33–36
Eeg-Olofsson O, Al-Zuhair AGH, Teebi AS et al. A boy with Rett syndrome? Brain Dev 1990 12: 529–532
Topçu M, Topaloglu H, Renda Y et al. The Rett syndrome in males Brain Dev 1991 13: 62
Hoffbuhr K, Devaney JM, LaFleur B et al. MeCP2 mutations in children with and without the phenotype of Rett syndrome Neurology 2001 56: 1489–1495
Akyerli C, Sayi A, Kocoglu RS, Cimbis M, Topcu M, Ozcelik T . Analysis of MECP2 gene mutations in Turkish Rett syndrome patients Eur J Hum Genet 2001 9 suppl. 1: P1450
Trappe R, Laccone F, Cobilanschi J et al. MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin Am J Hum Genet 2001 68: 1093–1101
Repas-Humpe LM, Humpe A, Lynen R et al. A dispermic chimerism in a 2-year-old Caucasian boy Ann Hematol 1999 78: 431–434
Maddalena A, Sosnoski DM, Berry GT, Nussbaum RL . Mosaicism for an intragenic deletion in a boy with mild ornithine transcarbamylase deficiency New Engl J Med 1988 319: 999–1003
Bakker E, Veenema H, Den Dunnen JT et al. Germinal mosaicism increases the recurrence risk for “new” Duchenne muscular dystropy mutations J Med Genet 1989 26: 553–559
Leuer M, Oldenburg J, Levergne J-M et al. Somatic mosaicism in hemophilia: A fairly common event Am J Hum Genet 2001 69: 75–87
Gartler SM, Francke U . Half Chromatid Mutations: Transmission in Humans? Am J Hum Genet 1975 27: 218–223
Kerr AM, Nomura Y, Armstrong D et al. Guidelines for reporting different clinical features in cases with MECP2 mutations Brain Dev 2001 23: 208–211
Acknowledgements
We would like to express our gratitude to the family for their help with this project. We thank Dr Uta Francke for critical reading of the manuscript, Drs Ergül Tunçbilek and Dilek Aktaş for performing the cytogenetic analysis, Dr Göknur Haliloğlu for help in obtaining patient samples, and Emre Sayan, Tolga Çağatay, Tülay Arayıcı for dosage analysis experiments and DNA sequencing. This work was supported by Bilkent University, and TÜBİTAK.
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Topçu, M., Akyerli, C., Sayı, A. et al. Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy. Eur J Hum Genet 10, 77–81 (2002). https://doi.org/10.1038/sj.ejhg.5200745
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DOI: https://doi.org/10.1038/sj.ejhg.5200745
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