Mutations in the methyl-CpG-binding protein 2 gene (MECP2) are identified in the 
majority of females with Rett syndrome (RTT), an X-linked dominant 
neurodevelopmental disorder. We searched for mutations by sequencing the MECP2 
coding region in 45 sporadic cases (35 with classic RTT, eight with variant 
forms and two males) and in seven families with two or more affected females. 
Following our previous report of mutations in two families and eight sporadic 
cases, we here present 18 additional mutations. We found 13 single nucleotide 
substitutions, all of which are C-->T transitions at CpG hot spots. Frameshift 
mutations, leading to premature termination of translation, include two single 
guanine (G) nucleotide deletions from a stretch of contiguous Gs, a novel four 
nucleotide deletion, a novel 32 nucleotide deletion in the C-terminal domain and 
a novel complex duplication/deletion rearrangement in the same region. When 
X-chromosome inactivation patterns were compared in 16 MECP2 mutation-positive 
and 23 mutation-negative samples, no significant differences were observed. The 
mutational spectrum in our subject population is similar to studies from around 
the world. Of over 300 MECP2 mutations reported, two-thirds are truncating 
mutations and one-third are missense mutations, mostly in the methyl-binding 
domain. Nearly 70% of all identified mutations are C-->T transitions at one of 
eight CpG hot spots, and about 10% are intragenic deletions or complex 
rearrangements that lead to frameshifts in the C-terminal region. The rate of 
mutation detection in the MECP2 coding region ranges from 70 to 85% in 
clinically diagnosed RTT and is much lower in diagnostic variants.