A female patient with adolescent-onset progressive myoclonus epilepsy carrying a truncating MECP2 mutation.

BACKGROUND: MECP2 is a well-known causative gene for Rett syndrome but other phenotypes have also been reported. Here, we report a case of a female patient with adolescent-onset progressive myoclonus epilepsy (PME) carrying a novel truncating mutation in the MECP2 gene. CASE REPORT: The patient was a 29-year-old woman with infantile-onset intellectual disability of unspecified cause. She had demonstrated slow but steady development with moderate intellectual disability until the age of 16, when she started having epileptic seizures. Her epilepsy progressed intractably with multiple seizure types accompanied by myoclonus, tremor, and gradual regression. She is currently apathetic and requires extensive assistance in all aspects of life. After an extensive work-up for underlying diseases for PME turned out negative, whole-exome sequencing revealed a de novo 113-bp deletion and 3-bp insertion in MECP2, a variant of NM_004992.4:c.1099_1211delinsGGG, p.(His367Glyfs*32). CONCLUSIONS: The clinical presentation of this case was inconsistent with Rett syndrome, and the rapid regression in the patient's twenties was considered characteristic. Mutations of MECP2 may result in variable neurodevelopmental phenotypes and may also be considered a causative gene for adolescent-onset PME.

Enhancement of MT synthesis by leptin in fasted mice.

It is known that metallothionein (MT) synthesis occurs in the liver in various stressful situations such as immobilization and fasting. However, the mechanism of MT synthesis in stressful situations is not fully understood. In this study, we examined the involvement of leptin, the obese gene product, in MT synthesis induced by fasting stress. Despite an increase in hepatic MT levels induced by 24-hr fasting in wild-type mice, both wild-type and MT-null mice showed decreases in plasma leptin levels after 24 hr of fasting. Hepatic MT levels increased to levels comparable with that in control mice in ICR, C3H, 129Sv and Balb/c mice fasted for 24 hr, and plasma leptin levels decreased significantly. Repetition of fasting and feeding in turn every 24 hr caused a gradual decrease in hepatic MT levels after the fasting period. In contrast, the reduced plasma leptin levels increased after the fasting period with repetition of fasting-feeding cycles. The findings indicate that there is an adaptation to starvation. On the other hand, subcutaneous leptin infusion in fasted mice via an osmotic pump resulted in increases in hepatic MT levels compared to the levels in vehicle-treated mice after 24 hr of fasting. Only leptin infusion had no effect on hepatic MT levels. These results suggest that MT synthesis in fasting stress is not correlated with decrease in plasma leptin levels but that leptin itself is a potent inducer of MT in a fasting situation.