Relationship between RELN signaling pathway genes and language development of autism based on a cluster model. / RELNä¿¡å·é€šè·¯åŸºå› ä¸ŽåŸºäºŽèšç±»åˆ†æžæ¨¡åž‹çš„å­¤ç‹¬ç—‡è¯­è¨€å‘è‚²çš„å ³ç³».

OBJECTIVES: Autism is a neurodevelopment disorder with unclear etiology. High heterogeneity is one of the main issues in the etiological studies. This study explores the relationship between RELN signaling pathway related genes (RELN, VLDLR, LRP8, DAB1, CDK5, FYN) and language development of autism patients based on a cluster analysis model which is established to reduce the heterogeneity. METHODS: Autism children were recruited from 5 different medical/autism training institutes from Hunan, Shandong, and Henan provinces, and were divided into 2 parts according to the recruitment time: The first part was the training sample, which was recruited from October 2006 to May 2011, and the second part was the validation sample, which was recruited from July 2011 to May 2012. A two-step cluster analysis was performed to cluster 374 Chinese Han autism patients into different subgroups based on 2 parameters: Onset age of the first word and interval from the first word to the first phase. A Bayes discriminatory equation was established followed the cluster results. Then we used this equation to divide another 310 autism children into prior defined subgroups. After the genotyping data was screened, a single marker case-control association study was conducted. RESULTS: The cluster analysis clustered 374 samples into 3 subgroups. Onset ages of the first word in the Group A were (11.83±4.37) months and intervals from the first word to the first phase were (24.55±8.67) months; onset ages of the first word in the Group B were (12.17±3.46) months, intervals from the first word to the first phase were (7.07±3.79) months; onset ages of the first word of Group C were (30.94±7.60) months, intervals from the first word to the first phase were (4.73±4.80) months. The established equations based on the cluster analysis were YA=-14.442+0.525X1+0.810X2, YB=-4.964+0.477X1+0.264X2, YC=-19.843+1.175X1+0.241X2. Cross validated analysis showed that the false rate of the equation was 3.8%. A total of 341 single nucleotide polymorphism (SNP) in 6 genes passed the quality control. Before divided subgroups, none of these SNPs reached the significant P value (P>2.44×10-5, Bonferroni adjustment). However the result showed that rs1288502 of LRP8 in Group B was significantly different from the control group (P=6.45×10-6). CONCLUSIONS: Based on the cluster analysis of language development, we could establish a discriminatory equation to reduce heterogeneity of autism sample. The association test indicates that LRP8 genein RELN signaling pathway is related to a particular type of language development of autism patients.

Tuberous sclerosis complex with skin lesions as the initial presentation: A case report and multidisciplinary discussion. / 1例以皮肤损害为首发症状的结节性硬化症并多学科讨论.

We reported a case of tuberous sclerosis complex with facial angiofibroma as the initial presentation and conducted a multidisciplinary discussion. The patient, a young female, was admitted to the Department of Dermatology for cosmetic purpose. After the examination, she was found to have multiple system involvement, including a large renal angiomyolipoma pressing on the liver. She never had any subjective symptom. After consultation by the multidisciplinary team of tuberous sclerosis complex, the patient was treated with everolimus orally and followed up regularly. It is suggested that dermatologists should pay attention to the systemic involvement of patients with tuberous sclerosis complex. Early intervention can prolong the life of patients and improve their life quality. Multidisciplinary collaboration for lifelong disease management is the key to enhance the diagnosis and treatment for tuberous sclerosis complex and enhance the prognosis of patients.

Comparison of demographic characteristics and psychiatric comorbidity among methamphetamine-, heroin- and methamphetamine-heroin co- dependent males in Hunan, China.

BACKGROUND: There is little research of psychiatric comorbidity differences among people with different types of drug dependence in Chinese population. We explored demographic and comorbid psychiatric differences among methamphetamine- dependent males (MDs), heroin-dependent males (HDs) and methamphetamine and heroin co-dependent males (M/HDs) in Hunan province, China. METHODS: A cross-sectional, structured and clinical interview method was used to examine differences in DSM-IV-TR Axis I Disorders among 346 MDs, 698 HDs and 247 M/HDs from three compulsory rehabilitation centers and two voluntary rehabilitation centers in Hunan. RESULTS: MDs and M/HDs were younger, more likely to choose inhalation administration, less likely to have a family history of substance use, less likely to have undergone detoxification treatment, had higher incomes and shorter duration of drug use than HDs. Overall, methamphetamine-dependence related to higher rates of current and lifetime psychotic disorders, lifetime hallucinogen use disorders. Heroin-dependence related to higher rates of current and lifetime substance-induced mood disorders, sedative/hypnotic/anxiolytic and other drug use disorders and current alcohol use disorder. For M/HDs, they were more likely to have any other lifetime substance use disorders than MDs and HDs. CONCLUSIONS: There were substantial differences in epidemiological characteristics and comorbidity among MD, HD and M/HD groups, which highlights the urgent need to develop treatment services and policies for drug-specific users in China.

CHN2 Promoter Methylation Change May Be Associated With Methamphetamine Dependence.

BACKGROUND: Methamphetamine (MA) abuse is becoming increasingly serious in China. The mechanism of MA dependence remains unclear. CHN2 gene encodes chimeric protein-2 that regulate axonal pruning via the Rac-GTPase system and play a pivotal role in the formation of nervous circuits. Genetic studies suggest that the polymorphism of the CHN2 gene was related to substance dependence. AIMS: The aim of this study was to investigate the association between the methylation of CHN2 gene promoter with MA dependence. METHODS: According to SCID-I (Structured Clinical Interview for DSM-IV Axis I Disorders, SCID-I) used for investigating MA dependence, 224 male MA addicts were recruited into the case group. In addition, 109 healthy men were recruited into the control group. Blood samples were collected with the purpose of detecting the methylation levels of CHN2 gene promoter by methylight qPCR. The association between the methylation of CHN2 gene promoter with MA dependence was analyzed. RESULTS: The mean (sd) methylation levels of CHN2 gene promoter in the case group were significantly higher than in the control group, which were 2795.55 (733.19) and 1026.73 (698.73), respectively, showing significant differences between the two groups (t=21.25, p<0.001). Pearson analysis showed no significant correlation between the methylation levels of CHN2 promoter and other factors (the age of initial MA use, the duration of MA use, combination with K powder, tobacco and alcohol). CONCLUSIONS: The abnormal methylation of CHN2 gene promoter was significantly correlated with MA dependence.