[Role of mitochondrial lesion in pathogenesis of sporadic rett syndrome].

OBJECTIVE

To investigate the role of mitochondrial lesion in children with Rett syndrome (RTT).

METHODS

The platelets from 6 cases with Rett syndrome and 9 normal controls were fused with mitochondrial DNA-lacking rho degrees cell by polyethylene glycol-mediated fusion technique. The oxygen free radical was evaluated by the polarography with substrates of vitamine C and TMPD (N, N, N', N'-tetramethyl-p-phenlene diamine). The rate of apoptosis was determinated by flow cytometry. The apoptosis was observed by electronic microscope and TUNEL method. The t test between groups was adopted in study.

RESULTS

In RTT patients, the anticyano-respiration significantly increased by 23% (t = 4.76, P < 0.01). After 6-hour coincubation with 100 micromol/L H(2)O(2), the rate of apoptosis is (3.6 +/- 1.1) % in normal control, and (9.9 +/- 2.7) % in RTT group with significant difference (t = 6.30, P < 0.01), the existence of apoptosis was confirmed by electronic microscope and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL).

CONCLUSION

After mitochondrial DNA transfer, the oxygen free radical increased in mitochondrial respiratory chain in cybrids of RTT children. RTT cybrid cell lines demonstrated an increased sensitivity to H(2)O(2)-induced apoptotic cell death as compared to control cybrids. The mitochondrial lesion might play a role in the pathogenesis of Rett syndrome.