MECP2 mutations in Serbian Rett syndrome patients.
BACKGROUND
Rett syndrome is a severe neurodevelopmental X-linked dominant disorder affecting 1/15,000 girls worldwide. Eight years ago, the MECP2 gene was associated with the devastating clinical features observed in Rett syndrome patients.


OBJECTIVE
To investigate the spectrum and the frequency of MECP2 mutations in Serbian Rett syndrome patients.


METHODS
We screened the MECP2 coding region by conventional mutational screening (single-strand conformation polymorphism/sequencing) in 24 patients of Serbian origin and in their 41 unaffected family members. In search for gene dosage alterations in seemingly mutation-negative girls, we developed a new, specific quantitative PCR method.


RESULTS
Nineteen patients (79%) carried MECP2 mutations, five of which were novel (one nonsense mutation, one duplication and three deletions). Fourteen previously described disease-causing sequence changes and one polymorphism were also detected. Detailed case reports are given for the carriers of the novel mutations. Large MECP2 rearrangements cause Rett syndrome in a significant number of girls without 'classic' mutations in this gene. Therefore, we developed a specific quantitative PCR method, covering MECP2 exons 3 and 4, which previously has not been used for screening. No dosage alterations of the two exons were found in the four tested mutation-negative girls.


CONCLUSIONS
This is the first genetic study of Rett syndrome in Serbian patients describing the MECP2 mutational and phenotypic spectrum in this population. Detailed clinical descriptions of this ethnically homogeneous patient population add to our knowledge of genotype/phenotype correlations in this severe condition.
Djarmati
A
A
Faculty of Biology, University of Belgrade, Belgrade, Serbia. ana.djarmati@neuro.uni-luebeck.de
Dobricić
V
V
Kecmanović
M
M
Marsh
P
P
Jancić-Stefanović
J
J
Klein
C
C
Djurić
M
M
Romac
S
S
D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D015518:Rett Syndrome / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D012737:Sex Factors; D015022:Yugoslavia / Q000208:ethnology
D005819:Genetic Markers; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2