Sažetak Mutation in the MECP2 gene located on the Xq28 chromosome can cause Rett syndrome, the most common cause of intellectual
disability in females. In addition to classic form, the mutations in MECP2 could result in atypical Rett syndrome and mild learning
disabilities in females. To date, more than 390 pathogenic mutations have been described, and eight most commonly occurring
account for more than 50% of all mutations. C-terminal domain of the gene is prone to small deletions (20-100 bp) that account for
7% of pathogenic mutations. More recently, large deletions (kilobases in size) that delete whole exons have been identifi ed. These are
more commonly found in females with classic (8%) than atypical Rett syndrome (3%). The aim is to present a recent molecular
testing strategy of the MECP2 gene in female patients with clinical diagnosis of Rett syndrome. Bidirectional sequencing of the entire
MECP2 coding region detects disease-causing mutations in approximately 80% of individuals with classic Rett syndrome. Frequent
mutations in exons 3 and 4 in MECP2 are tested by screening methods based on PCR and sequencing, and large rearrangements are
tested by quantitative methods. In conclusion, the spectrum of phenotypes in MECP2-related disorders includes not only classic and
atypical Rett syndrome, but also other neurologic disorders. Besides, in the minority of Rett patients, mutations in MECP2 have not
been identifi ed. Therefore, the identifi cation of MECP2 mutation can support a clinical diagnosis, but cannot exclude it completely.
Molecular testing is particularly important in elucidating cases of atypical Rett. The molecular testing strategy of Rett syndrome
includes: 1) sequencing of MECP2 coding region; 2) analysis of MECP2 noncoding region; 3) screening for large rearrangements in
MECP2; and 4) analysis of CDKL5 and FOXG1 genes involved in the atypical forms of Rett syndrome.