De novo deletion in MECP2 in a monozygotic twin pair: a case report

We investigated 13 year old, monozygotic twin females with RTT and some noticeable differences in development using a combinatorial approach of sequencing and Taqman assay. Monozygosity status of the twins was confirmed by informative microsatellite markers.The twins shared a de novo deletion in exon 3 in the MBD domain of MECP2. To the best of our knowledge, this is only the second report of genetic analysis of a monozygotic twin pair.Rett Syndrome (RTT; MIM # 312750) is a severe progressive neurodevelopmental disorder that predominantly affects females. It has an estimated global prevalence of approximately one in 10,000-15,000 female births [1,2] and one in 100,000 male births [3,4]. Typical/classical RTT is characterized by normal development up to the age of 7-18 months; then a period of developmental stagnation followed by rapid regression, deceleration of head growth, stereotypic hand movements, loss of speech and acquired motor skills. In contrast, atypical RTT refers to a subset of patients who do not meet all the criteria but manifest a variant form of the disease which exhibits heterogeneity in terms of age of onset, severity and clinical course [5,6]. Point mutations and insertion/deletion variations in MECP2 (Xq28) account for approximately 70-80% of cases with classic RTT [7,8] and a lower percentage of atypical cases [9-11]. Gross rearrangements in MECP2, which cannot be detected by sequencing or dHPLC, can be identified by a range of alternate methods such as Southern blot analysis [12,13], gene dosage assays with quantitative fluorescent PCR [14,15], and multiplex ligation-dependent probe amplification (MLPA) [16,17]. These methods contribute to unequivocal diagnosis of an additional ~10% of mutation negative cases [18]. Exons 3 and 4 in the MECP2 have been identified to be hotspots for rearrangements [1,2].A limited number of twin pairs with RTT, all clinically well characterized, have also been reported in literature. Some studies have described t