Detection of heterozygous deletions and duplications in the MECP2 gene in Rett syndrome by Robust Dosage PCR (RD-PCR)

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Abstract
Fifty to eighty percent of Rett syndrome (RTT) cases have point mutations in the gene encoding methyl‐CpG‐binding protein‐2 (MECP2). A fraction of MECP2 negative classical RTT patients has large heterozygous deletions. Robust Dosage PCR (RD‐PCR) assays were developed as a rapid, convenient and accurate method to detect large heterozygous deletions and duplications. A blinded analysis was performed for 65 RTT cases from Portugal by RD‐PCR in the coding exons 2‐4 of the MECP2 gene. Neither the patients with point mutations nor the non‐classical RTT patients without point mutation had a deletion or duplication. One of remaining eight female patients with classical RTT without point mutation had a heterozygous deletion. This is the first report of a deletion spanning the entire MECP2 gene. The deletion was confirmed by Southern blotting analysis and the deletion junction was localized 37kb upstream from exon 1 and 18kb downstream from exon 4. No duplications were detected. Our results suggest that RD‐PCR is an accurate and convenient molecular diagnostic method.

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