Abstract
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.
Keywords
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Article info
Publication history
Accepted:
February 6,
2001
Received in revised form:
February 2,
2001
Received:
September 25,
2000
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
