SUMMARY Rett syndrome (RTT) , an X-linked dominant neurodevelopmental disorder characterized by regression of language, stereotype hand movement and loss of purposeful hand use, is primarily caused by mutation of menthyl-CpG-binding protein 2 ( MECP2 ). The 76 kb human MECP2 is characterized by three sab'ent features; a very large intron 2 (60 kb) , an 8. 5 kb 3'-UTR with highly conserved regions and different polyadenylation sites, and a 40 kb intergenic region separating MECP2 from the nearest upstream gene. There are two isoforms of MeCP2, MeCP2el and MeCP2e2. The differences between the two isoforms, the function of the 3'-UTR and the long-range cis-regulatory sequences in the intergenic region were extensively studied. In contrast to initial report, recent studies show that MeCP2 binds not only to methylated promoters and silence transcription, but also to the sites outside of genes containing only a few of CpG islands. Furthermore, MeCP2 can function as both an activator and a repressor of transcription.

SUMMARY Lysosomal storage diseases are a group of genetic disorders that result from the defect in lysosomal function. Signs and symptoms are variable, it is difficult to diagnose this group of disease merely by the clinical manifestation. The diagnosis usually is made by measuring the activity of the corresponding enzyme. Gene mutational analysis is useful for the diagnosis of some of the lysosome storage diseases. The treatment has focused on the replacement of the defective enzyme responsible for the disease and the hematopoietic stem cell transplantation. Both of them have achieved exciting outcomes in some of the diseases.

Rett syndrome(RTT),an X-linked dominant neurodevelopmental disorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-binding protein 2(MECP2).The 76 kb human MECP2 is characterized by three salient features: a very large intron 2(60 kb),an 8.5 kb 3′-UTR with highly conserved regions and different polyadenylation sites,and a 40 kb intergenic region separating MECP2 from the nearest upstream gene.There are two isoforms of MeCP2,MeCP2e1 and MeCP2e2.The differences between the two isoforms,the function of the 3′-UTR and the long-range cis-regulatory sequences in the intergenic region were extensively studied.In contrast to initial report,recent studies show that MeCP2 binds not only to methylated promoters and silence transcription,but also to the sites outside of genes containing only a few of CpG islands.Furthermore,MeCP2 can function as both an activator and a repressor of transcription.Abstract:SUMM ARY Rett syndrome(RTT),an X-linked dom inant neurodevelopmental d isorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-bind ing protein 2(MECP2).The 76 kb humanMECP2is characterized by three salient features: a very large intron 2(60 kb),an 8.5 kb 3′-UTR with highly conserved regions and d ifferent polyadenylation sites,and a 40 kb intergenic region separatingMECP2from the nearest up-stream gene.There are two isoforms ofMeCP2,MeCP2e1 and MeCP2e2.The d ifferences between the two isoforms,the function of the 3′-UTR and the long-range cis-regulatory sequences in the intergenic re-gion were extensively stud ied.In contrast to initial report,recent stud ies show thatMeCP2 binds not only to methylated promoters and silence transcription,but also to the sites outside of genes containing only a few of CpG islands.Furthermore,MeCP2 can function as both an activator and a repressor of transcrip-tion.

OBJECTIVETo investigate the clinical features and genetic characteristics of patients with 3-hydroxy-isobutyryl-CoA hydrolase (HIBCH) gene mutations.

METHODThe clinical data of a patient with novel HIBCH mutations were collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center for Biotechnology Information and PubMed (up to December 2014) by using search terms" HIBCH", "3-hydroxy-isobutyryl-CoA hydrolase" or "beta-Hydroxyisobutyryl CoA Deacylase Deficiency". The clinical features, neuroimage and treatment of the patients with HIBCH gene mutations were studied.

RESULTThe patient was a girl who was born at term after an uneventful pregnancy to non-consanguineous healthy parents, she was hospitalized at 5 years and 5 months of age because of development delay for 5 years and 5 months and abnormal posture on the left of body for more than 10 days. The family history was unremarkable. Her psychomotor development was significantly delayed. Three times brain MRI between 2. 5 years and 5 years of age revealed bilateral symmetrical lesions in basal ganglia. At the age of 5 years and 5 months, she presented with acute encephalopathy and severe extrapyramidal symptoms preceded by fever. At that time, her brain MRI revealed aggravated lesions in bilateral basal ganglia, new lesions in the midbrain cerebral peduncle and pons, and cerebellar atrophy. The results of biochemical tests were normal. A novel compound heterozygous mutation of HIBCH gene, c. 1027C > G, p. H343D and c. 79-1G > T, splicing, were found in the parent. Further study showed that c. 1027 C > G mutation was inherited from her father and c. 79-1 G > T from her mother. Her symptoms were mitigated after "cocktail" therapy and symptomatic treatment. Repeated brain MRI revealed that the lesion in basal ganglia got better, the lesions in brain stem disappeared. Literature relevant to HIBCH published all around the world was reviewed, no Chinese cases with HIBCH gene mutations had been reported, 6 foreign cases with HIBCH gene mutations were reported. Among them, 5 patients were diagnosed as Leigh-like syndrome, with progressive neurodegenerative course, and symmetrical basal ganglia lesions on brain MRI. Another case was reported in 1982, with developmental delay and various physical malformations without data on his brain MRI. HIBCH gene mutational analysis showed that 4 cases had homozygous mutations, which were c. 950G > A (p. G317E) in two brothers, c. 219 _220insTTGAATAG (p. K73fsX86) and c. 1128_1129insT (p. K377X) respectively. Three of them died before 3 years old. Two cases had compound heterozygous mutations: c. 365A > G (p. Y122C) and IVS2-3C > G (p. R27fsX50); c. 517 + 1G > A and c. 410C > T (p. A137V). They were alive at the time of the report.

CONCLUSIONPatients with HIBCH gene mutation mainly presented as Leigh-like syndrome both in clinical manifestation and in neuroimage. HIBCH gene mutational analysis should be performed on children with Leigh-like syndrome, if the mutations of known genes of Leigh syndrome were negative.

Abnormalities, Multiple ; diagnosis ; genetics ; Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; Child ; Child, Preschool ; China ; DNA Mutational Analysis ; Female ; Heterozygote ; Homozygote ; Humans ; Infant ; Leigh Disease ; diagnosis ; genetics ; Magnetic Resonance Imaging ; Male ; Mutation ; Siblings ; Thiolester Hydrolases ; deficiency ; genetics

SUMMARY To demonstrate the clinical manifestation, diagnosis and treatment of myoclonus epilepsy with ragged-red-fibers ( MERRF) , a case of MERRF was presented with review of the literature. A 4-year-7-month-old girl was diagnosed with MERRF. She had tremor, fatigue and developmental delay for more than 2 years. Laboratory tests showed that the serum and urine lactic acid and pyruvic acid increased significantly. Electroencephalogram showed diffuse and focal spike slow wave and slow wave in right central and parietal regions. Electromyogram showed neurological damage. Gene mutational analysis showed mtDNA 8344 A>G mutation. The mutational rate was 78%. Mitochondrial disease MERRF syndrome was diagnosed. Cocktails therapy with vitamins B1, B6, B12, L-carnitine, and coenzyme Q10 was administra-ted to the patient. MERRF is a rare disease. The diagnosis can be made by gene mutational analysis. Cocktail therapy may slow down the deterioration of the disease. Gene therapy is still experimental.

Objective To explore the clinical features and pathogenic genes of sialidosis. Methods The clinical data and genetic test results of a family with sialidosis were retrospectively analysed. Results The proband was a 13-year-old girl who presented with limb pain at age 7, followed by progressive vision loss and convulsive seizure. In addition, she also had the sign of ataxia. Fundus examination showed optic atrophy in her eyes. Visual evoked potential showed that the latency of binocular P100 was significantly prolonged. The elder brother of the proband showed similar manifestation. PCR was used to amplify the exons and exon-intron boundaries of the NEU1 gene, and DNA direct sequencing was used to detect the mutation in this gene. It was found that both proband and her brother carried two known pathogenic heterozygous mutations in the NEU1 gene, c.239C>T (p.P80L) and c.544A>G (p.P80L) respectively from both their mother and father of normal phenotype. Conclusion The causative mutation of the NEU1 gene in the family of sialidosis has been defined.

Methyl-CpG-binding protein 2 gene (MECP2; OMIM 300005) is located at chromosome Xq28. Mutations of the gene including point mutation, duplication and deletion can lead to severe neurodevelopmental disorders. The disease caused by duplication of the entire MECP2 gene, named as MECP2 duplication syndrome, is mostly seen in males. The clinical manifestation of this syndrome include mental retardation, hypotonia, poor speech development, recurrent infection, progressive spasticity, epilepsy, autism or autistic features with or without midface hypoplasia. Most patients have inherited the duplication from their unaffected mothers, with only a few cases having de novo mutation. Females with duplicated MECP2 gene are typically asymptomatic because of a skewed X chromosome inactivation (XCI) pattern. Proposed mechanisms of this genomic rearrangement include fork stalling and template switching (FoSTeS) and microhomology mediated break-induced replication (MMBIR). Since no effective treatment is available for this disease, proper genetic counseling and prenatal diagnosis for the high risk families are crucial.
Animals ; Female ; Gene Duplication ; Humans ; Male ; Mental Retardation, X-Linked ; genetics ; metabolism ; Methyl-CpG-Binding Protein 2 ; genetics ; metabolism

The individual intervention control of risk factors in high-risk population is one of key preventive measures of chronic disease.A total of 312 volunteers consulted physicians in one selected community.And 23 high-risk individuals of chronic disease were screened.The physicians customized the limit or requirement of diet,activity,tobacco and alcohol for each individual and made interventions of life behaviors according to the plans.The results showed that physical state of 20 (87％) of them converted from high-risk to health after interventions.Therefore customized control plan of individual risk factors is an effective control method of chronic disease.

AIM: To study the effects of norepinephrine preconditioning(NE-P) and ischemic preconditioning (IP)on apoptosis and Bcl-2, Bax expression in rat myocardial cells in myocardial ischemic reperfusion (I/R). METHODS: The model of rat ischemic-reperfusion was used to conduct NE-preconditioning. Apoptotic myocytes were detected with TUNEL. Bcl-2, Bax expression were detected with immunohistochemistry. RESULTS: The rate of apoptosis cells in I/R group was higher, the rate of apoptosis cells in NE-P group and IP was lower significantly than that in I/R group( P0.05). CONCLUSION: NE-P reduced myocyte apoptosis by I/R in rats; The expression of Bcl-2 ,Bax genes played an important role in myocardial apoptosis.

Objective To compare the effect of hyperfractionation radiotherapy combined with hepatic artery catheterization chemotherapy and hepatic artery ligation (group A, 65 patients) with conventional fractionation radiation combined with hepatic artery catheterization chemotherapy and hepatic artery ligation (group B, 65 patients) for unresectable primary liver cancer.Methods A total of 130 stage Ⅱprimary liver patients confirmed by pathology and evaluated as unresectable by exploratory laparotomy were divided evenly into group A and group B by the sequence of exploration. The two groups were comparable in age, sex, tumor type and positive fetal protein (AFP). Group A patients were treated by hepatic artery chemotherapy (PDD, 10 mg/day) 6 days a week with hepatic artery ligation followed by hyperfractionation radiotherapy (250 cGy/f, bid) 3 days a week with the scheme alternated weekly. Group B patients were treated by conventional fractionation radiotherapy with the same scheme of chemotherapy as group A. The total dose of PDD and radiotherapy for both groups were 240 mg and 45Gy. Results The AFP level was reduced to half in 89.7% of patients in group A and 67.6% in group B. The 1 , 3 and 5 year survival rates were 90.8%, 63.1%, 23.1% for group A and 73.9%, 41.5% 9.2% for group B, the difference was statistically significant (P0.05). Conclusions Hyperfractionation radiotherapy combined with hepatic artery catheterization chemotherapy and hepatic artery ligation is an effective and reasonable therapeutic scheme for unresectable liver cancer. It can effectively relieve symptoms, reduce the tumor, increase second surgical resection rate and prolong the survival. At the same time, the operation is simple and relatively easy.