Objective:To determine the genetic causes of dystonic cerebral palsy (DCP) of unknown etiology by using whole exome and mitochondrial gene detection methods, and to analyze clues for early identification of DCP.Methods:This was a retrospective analysis of clinical data describing 21 children with unknown etiology and DCP-like phenotypes. It involved collecting a detailed medical history, biochemical testing, neuroimaging, electroencephalography and hematuria metabolic screening. Peripheral blood was collected from the children, their parents and their siblings. Genomic DNA was extracted, and whole exome and/or mitochondrial gene sequencing was performed to obtain variant sites and annotations. The candidate variants were verified by Sanger sequencing.Results:No clear perinatal risk factors were found in the 21 cases, though there was 1 case of family history. Laboratory tests found increased lactic acid in 3 and abnormal thyroid function in 2 cases. The neuroimaging showed lesions in the basal ganglia in 2 cases, delayed myelination in 6 cases, sometimes with cortical dysplasia, a wide extracerebral space and/or a thin corpus callosum. The images of 11 of the children were normal. Later follow-up showed changes in the brain magnetic resonance images (MRIs) of 2 of the children. Pathogenic or likely pathogenic candidate variants were identified in 15 of the 21 children (71%) within 12 genes: TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MT- ATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 or NACC1. Fifteen of the children received a precise diagnosis. Genetic testing found heterozygous variants of ATP1 A2, SPR, ATP1 A3, MED13 L or NR4 A2 genes in the remaining six children, all of which were non-pathogenic variants. Conclusions:The absence of perinatal high-risk factors, a positive family history, and a normal or progressive brain MRI can be used as early clues to identify atypical DCP cases. TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MTATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 and NACC1 variants belong to the spectrum of DCP-related pathogenic genes, and attention should be paid to the interpretation of genomic analysis results.

Objective:To determine the genetic causes of dystonic cerebral palsy (DCP) of unknown etiology by using whole exome and mitochondrial gene detection methods, and to analyze clues for early identification of DCP.Methods:This was a retrospective analysis of clinical data describing 21 children with unknown etiology and DCP-like phenotypes. It involved collecting a detailed medical history, biochemical testing, neuroimaging, electroencephalography and hematuria metabolic screening. Peripheral blood was collected from the children, their parents and their siblings. Genomic DNA was extracted, and whole exome and/or mitochondrial gene sequencing was performed to obtain variant sites and annotations. The candidate variants were verified by Sanger sequencing.Results:No clear perinatal risk factors were found in the 21 cases, though there was 1 case of family history. Laboratory tests found increased lactic acid in 3 and abnormal thyroid function in 2 cases. The neuroimaging showed lesions in the basal ganglia in 2 cases, delayed myelination in 6 cases, sometimes with cortical dysplasia, a wide extracerebral space and/or a thin corpus callosum. The images of 11 of the children were normal. Later follow-up showed changes in the brain magnetic resonance images (MRIs) of 2 of the children. Pathogenic or likely pathogenic candidate variants were identified in 15 of the 21 children (71%) within 12 genes: TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MT- ATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 or NACC1. Fifteen of the children received a precise diagnosis. Genetic testing found heterozygous variants of ATP1 A2, SPR, ATP1 A3, MED13 L or NR4 A2 genes in the remaining six children, all of which were non-pathogenic variants. Conclusions:The absence of perinatal high-risk factors, a positive family history, and a normal or progressive brain MRI can be used as early clues to identify atypical DCP cases. TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MTATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 and NACC1 variants belong to the spectrum of DCP-related pathogenic genes, and attention should be paid to the interpretation of genomic analysis results.

This study investigated the effects of bile duct ligation(BDL)-induced liver injury on the function and expression of organic cation transporter 1/2(OCT1/2)at blood brain barrier(BBB)and their potential mechanisms.BDL rat model was constructed,and physiological and biochemical parameters,BBB integrity,cortical OCT1/2 protein expression and function,and plasma chenodeoxycholic acid(CDCA)level were then examined by kits,Western blot,and LC-MS.Physiological and biochemical parameters,plasma bile acid levels,and cortical OCT1/2 protein expression were determined in rats after ig administration of CDCA for 14 d.The results showed that serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP)levels increased,plasma CDCA level increased,the brain-to-blood concentration ratio(Kp)of amantadine decreased,while cortical Claudin-5 and Occludin did not significantly change,OCT1 expression was downregulated,while OCT2 did not significantly change in BDL rats.Serum AST,ALT,and ALP levels did not significantly change,plasma CDCA level increased,cortical OCT1 expression was downregulated,and OCT2 did not significantly change in rats after ig administration of CDCA.This study suggests that downregulation of OCT1 function and expression at BBB of BDL rats is related to elevated CDCA in plasma.

Objective To investigate the blood fatty levels in different genotypes of matrix metalloproteinases (MMP) and the carotid atherosclerosis (CAS) in patients with essential hypertension (EH).Methods Four hundred and eighty-eight cases of Han and Uygur in patients with EH were selected,and MMP-2-735 C/T and MMP-3-1171 5A/6A polymorphism was measured by polymerase chain reactionrestriction fragment length polymorphism.They were divided into two groups:EH with CAS group (CAS group,293 cases,Han 171 cases,Uygur 122 cases) and EH without CAS group (NS group,195 cases,Han 105 cases,Uygur 90 cases).Blood fatty factors were analyzed according to the different MMP genotypes.Results According to MMP-2 genotypes,in Hart CAS group,the low density lipoprotein cholesterol (LDL-C) levels in MMP-2 CT+TT genotypes were significantly higher than those in CC genotype(P ＜ 0.05),and high density lipoprotein cholesterol levels were significantly lower than those in CC genotype(P ＜ 0.05); In Uygur CAS group,the triglyceride levels in MMP-2 CT+TT genotypes were significantly higher than those in CC genotype(P ＜ 0.05).According to MMP-3 genotypes in Han NS group,the total cholesterol and LDL-C levels in 6A/6A genotype were significantly higher than those in 5A/5A+5A/6A genotypes (P ＜ 0.05).Conclusion The blood fatty levels are different in patients with different MMP genotypes,which may probably influence the CAS.