Deleterious mutations in exon 1 of MECP2 in Rett syndrome.

The MECP2gene is responsible for 80-85% of typical cases of Rett syndromewith deleterious mutationsaffecting exons3 and 4. Recently, an alternate transcript including exon1 was discovered with a new protein isoform(MeCP2_e1) much more abundant in brain. We screened exon1 of MECP2for mutations and for large rearrangements in a panel of 212 typical cases of Rett syndromeand one family case with atypical Rett syndrome. We identified two deleterious mutations(c.48_55dup and c.62+2_62+3del) and four large rearrangements encompassing exon1 of MECP2. We also identified the c.16_21dup alteration formerly reported as c.3_4insGCCGCC and give additional support to classify this sequence variation as polymorphic. In our large panel of typical Rett, mutations affecting exon1 of MECP2represent 1% of the deleterious alleles. This study confirms that mutations in exon1 of MECP2are a rare cause of Rett syndrome.