| dc.description.abstract | Rett Syndrome (RTT) is a progressive X-linked dominant childhood neurodevelopmental
disorder, affecting 1/10,000-15,000 girls. The disease-causing gene was identified as
MECP2 on chromosome Xq28, and mutations have been found in approximately 80% of
patients diagnosed with RTT. We screened for eight recurrent MECP2 mutations
(R106W, P152R, T158M, R306C, R168X), one rare mutation (F155S) and one
polymorphism (E397K) in 63 RTT patients divided into four groups as classic-RTT
(n=43), variant-RTT (n=14), male-RTT (n=4), and familial-RTT (n=2). We identified
the recurrent mutations in 18 cases. These are three R106W, two P152R, five T158M,
five R306C, and three R270X mutations. R168X and F155S were not detected in our
patients. Only one patient had the E397K polymorphism who also had the R306C
mutation. All these mutations were confirmed via sequencing analysis. In exon 4 of
MECP2, several deletion types of mutations are known. By PCR analysis, two patients
were found to have an approximately 44 bp deletion in exon 4. Also, a novel mutation –
T197M– was identified in one of the patients. We identified a boy affected by RTT who
is mosaic for the R270X mutation, and had a normal male karyotype. This result show
that a recurrent MECP2 mutation could lead to a similar phenotype in females and males,
if the male is a mosaic for the mutation in his somatic cells. MECP2 mutation frequency
for the four groups is as follows: 37.2% for the classic-RTT, 28.57% for the variantRTT,
and 25% for the male-RTT groups. No mutation was found in the familial group.
We could not find a consistent correlation between the clinical symptoms and the type of
mutations or the X chromosome inactivation patterns of the patients. | en_US |
