Abstract for presentation at 11th International Congress of Human Genetics

Rett syndrome (RTT; MIM 312750) is an X-linked dominant neuro-developmental disorder that almost exclusively affects girls. It is caused by mutations in the MECP2 gene located on Xq28. Mutations are identified in 80% of classic RTT patients by DNA sequencing, which is prone to miss large deletions. Several studies have reported large deletions within the MECP2 gene using various methods. We have studied 30 Chinese classical RTT patients without a defined MECP2 mutation using multiplex ligation-dependent probe amplification (MLPA). MECP2-MLPA was carried out using kit P015C (MRC-Holland, Amsterdam, Netherlands). Analysis of X chromosome inactivation (XCI) was also performed on the androgen receptor gene. We detected 11 cases with large deletions of the MECP2 gene in the 30 Chinese classical RTT patients (36.6%)(Table 1). Six deletions involved two exons: five involved exons 3 and 4 and one involved exons 1 and 2. Four deletions involved only part of exon 4. In one case, the flanking IRAK gene was deleted along with the exons 3 and 4 of the MECP2. XCI study showed that 7 patients were informative and 4 were not informative (Table 1). This is the first report on the frequency of large deletions of the MECP2 gene in Chinese patients with classical RTT, with comparison of the clinical features and molecular defects between Chinese and Caucasian patients with RTT. The detection rate of 36.6% (11/30) is comparable with the reported data (20-38%). Large deletions frequently involve either exon 4 or both exons 3 and 4 of the MECP2 gene, similar to the observations of other studies. The range of the clinical severity score is 4 to 8 in our patients, who did not display additional congenital anomalies. We did not find a phenotypic difference between patients with deletions involving different exons, nor with the degree of XCI (Table 1). In addition, we did not find correlation between the degree of XCI and the type or size of the MECP 2 deletion (Table 1). Consistent with previous studies, we cannot establish any specific genotype /phenotype correlation in our cohort of Chinese patients with classical RTT.