Original article| Volume 23, ISSUE 4, P212-215, July 2001

Mutational analysis of MECP2 in Japanese patients with atypical Rett syndrome


      Rett syndrome (RTT) is one of the most common neurodevelopmental disorders in females. Recently, this disease was found to be linked with mutations in the methyl-CpG-binding protein 2 gene (MECP2) and various mutations have been reported. To explore the spectrum of phenotypes resulting from MECP2 mutations, we searched for mutations in the MECP2 of 20 Japanese patients who had more than five of the criteria necessary for RTT diagnosis proposed in 1988 (The Rett Syndrome Diagnostic Criteria Work Group, Ann Neurol 23 (1988) 425) and compared the phenotype between patients with and without mutation by giving a score to each diagnostic criterion. We found four missense mutations (T158M, R133C, Y120D, and R306C), two nonsense mutations (R168X and R270X), one frameshift (726delAAAG) mutation, and one polymorphism (A201V) in ten patients (50%). This included two novel mutations (726delAAAG and Y120D). All mutations were found in the highly conserved methyl-binding and transcription repression domains. Comparison of the mean total diagnostic criterion score of the groups with and without mutation did not reveal any statistically significantly difference (P=0.28). The only difference between the groups, which was of borderline significance (P=0.051), was the sum of the scores for diagnostic criteria 2 (apparently normal psychomotor development through the first 6 months) and 5 (loss of acquired purposeful hand skills between the ages of 6 and 30 months). From these results, it is suggested that the clinical phenotype of RTT is variable and it is important to investigate the MECP2 genotype for patients having more than five criteria and not only in those who exhibit all RTT diagnostic criteria. The diagnosis of RTT is clinically difficult before 3 years of age, especially in atypical cases, but molecular analysis of the MECP2 will assist diagnosis in some patients.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • The Rett Syndrome Diagnostic Criteria Work Group
        Diagnostic criteria for Rett syndrome.
        Ann Neurol. 1988; 23: 425-428
        • Rett A
        Über ein eigenartiges hirnatrophisches Syndrom bei Hyperammoniamie in Kindesalter.
        Wein Med Wochenschr. 1966; 116: 723-728
        • 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
        • Comings D.E
        The genetics of Rett syndrome: the consequences of a disorder where every case is a new mutation.
        Am J Med Genet Suppl. 1986; 1: 383-388
        • Hagberg B
        Rett's syndrome: prevalence and impact on progressive severe mental retardation in girls.
        Acta Paediatr Scand. 1985; 74: 405-408
        • Witt-Engerstrom I
        • Gillberg C
        Rett syndrome in Sweden.
        J Autism Dev Disord. 1987; 17: 149-150
        • Kerr A.M
        • Stephenson J.B
        Rett's syndrome in the west of Scotland.
        Br Med J. 1985; 291: 579-582
        • Amir R.E
        • Van den Veyver I.B
        • Wan M
        • Tran C.Q
        • Francke U
        • Zoghbi H.Y
        Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
        Nat Genet. 1999; 23: 185-188
        • Cheadle J.P
        • Gill H
        • Fleming N
        • Maynard J
        • Kerr A
        • Leonard H
        • et al.
        Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location.
        Hum Mol Genet. 2000; 9: 1119-1129
        • Huppke P
        • Laccone F
        • Kramer N
        • Engel W
        • Hanefeld F
        Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients.
        Hum Mol Genet. 2000; 9: 1369-1375
        • Bienvenu T
        • Carrie A
        • de Roux N
        • Vinet M.C
        • Jonveaux P
        • Couvert P
        • et al.
        MECP2 mutations account for most cases of typical forms of Rett syndrome.
        Hum Mol Genet. 2000; 9: 1377-1384
        • Amir R.E
        • Van den Veyver I.B
        • Schultz R
        • Malicki D.M
        • Tran C.Q
        • Dahle E.J
        • et al.
        Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes.
        Ann Neurol. 2000; 47: 670-679
        • Amano K
        • Nomura Y
        • Segawa M
        • Yamakawa K
        Mutational analysis of the MECP2 gene in Japanese patients with Rett syndrome.
        J Hum Genet. 2000; 45: 231-236
        • Hagberg B.A
        • Skjeldal O.H
        Rett variants: a suggested model for inclusion criteria.
        Pediatr Neurol. 1994; 11: 5-11