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Evidence of somatic mosaicism for aMECP2 mutation in females with Rett syndrome: diagnostic implications
  1. Violaine Bourdona,
  2. Christophe Philippea,
  3. Thierry Bienvenub,
  4. Bernadette Koenigc,
  5. Marc Tardieud,
  6. Jamel Chellyb,
  7. Philippe Jonveauxa
  1. aLaboratoire de Génétique Médicale, CHU Nancy-Brabois, Avenue du Morvan, 54511 Vandoeuvre les Nancy, France, bLaboratoire de Génétique et Physiopathologie des Retards Mentaux-ICGM, Faculté de Médecine Cochin, Paris, France, cSite du Neuhof, Centre de Ressources en Matière de Déficiences Sensorielles et de Polyhandicaps Louis Braille - Raoul Clainchard - Auguste Jacoutôt, Strasbourg, France, dDépartement de Pédiatrie, Service de Neurologie, CHU Bicêtre, Le Kremlin Bicêtre, France
  1. Dr Jonveaux, p.jonveaux{at}

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Editor—Rett syndrome (RTT) (MIM 312750) is an X linked dominant neurodevelopmental disorder that occurs almost exclusively in females. Affected girls are considered to have a normal perinatal period followed by a period of regression, loss of acquired purposeful manual and speech skills, hand wringing, gait disturbance, and growth retardation.1 2

A gene for RTT has been identified in the Xq28 region which encodes the methyl-CpG binding protein 2 (MeCP2) involved in transcriptional silencing.3 4 This disorder most frequently occurs sporadically and results from a de novo mutation, although a few familial cases have been reported. Many studies5-16 have shown that the MECP2 gene is mutated in approximately 80% of patients with classical RTT and theMECP2 mutation spectrum includes missense, nonsense, and frameshift mutations, as well as larger rearrangements like deletions encompassing a few hundred bp.16 The failure to detect MECP2 mutations in the remaining 20% may indicate the presence of mutations in unexplored regions of the MECP2 gene, such as regulatory elements or non-coding regions, notably in the new first exon17 or in an additional RTT locus.

Here, we report for the first time mosaicism for a somaticMECP2 mutation found in two unrelated females affected with RTT. These two girls were diagnosed according to the international criteria of the Rett Syndrome Diagnostic Criteria Work Group.18

Case reports

The first patient (case 1) is 13 years old. She suffers from classical Rett syndrome with 7/9 of the necessary criteria, 4/8 of the supportive criteria, and none of the exclusion criteria.18More specifically, she had a normal neonatal period and head circumference at birth and a phase of social withdrawal at the age of 12 months when she lost purposeful hand skills and developed stereotypic hand movements, ataxia, and apraxia. She suffered from …

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