Objectives To explore the clinical features and diagnosis of LMNA-associated congenital muscular dystrophy. Methods The clinical data from a case of muscular dystrophy caused by LMNA gene mutation were retrospectively analyzed. The related literatures were reviewed. Results A 8-month-old female infant suffered from weakness of raising head, eyelid droop, and motor development retardtion. LMNA gene was sequenced for the infant, her parents and the older sister. Heterozygous mutation of c. 94_96 del AAG (p. K 32 del) was found in the infant leading to the diagnosis of LMNA- associated congenital muscular dystrophy. No mutation was found in the infant’s parents and her older sister. The literature review showed that all ofLMNA- associated congenital muscular dystrophy patients had LMNA gene mutation, more than 80% patients mainly presented with weakness of raising head and may accompany with weakness of proximal limb, motor development retardation, and weakness of axial muscle. Conclusions Mutation analysis of LMNA gene is conducive to the diagnosis of congenital muscular dystrophy.

Objective To investigate the molecular mechanism of calreticulin ( CRT) transcription induced by HBV and its viral proteins. Methods The human hepatocellular cell line, HepG2, was trans-fected with pHBV1. 3 and eukaryotic expression plasmids of HBV viral proteins, respectively. The expres-sion of CRT was measured after transfection. A reporter plasmid of CRT promoter was constructed to analyze the induction of CRT promoter by pHBV1. 3 and HBV viral proteins. Furthermore, two truncated and one C/EBPα site deficient mutants were constructed to evaluate the regulatory effects of HBx on CRT promoter. Fi-nally, HepG2 cells were transfected with HBx expression plasmids and the cellular localization of C/EBPαwas analyzed. Results In this study, pHBV1. 3 could significantly up-regulate the expression of CRT at mRNA and protein levels as well as enhancing the activity of CRT promoter. Among the seven HBV viral proteins, HBx could enhance the activity of CRT promoter and the expression of CRT at mRNA and protein levels. HBx could not induce the transcription of CRT when the C/EBPα binding site was deleted from the CRT promoter. The expression of HBx could promote the nuclear translocation of C/EBPα. Conclusion HBV and its viral protein HBx could up-regulate the CRT expression at transcriptional level. The transcrip-tional factor C/EBPα played a critical role in HBx-induced transcriptional activation of CRT.

Objective To investigate the clinical features and genetic basis of cryopyrin-associated periodic syndrome (CAPS). Methods The clinical manifestations, laboratory tests, and genetic tests of one case of CAPS were retrospectively analyzed. The related literatures were reviewed. Results A 7 year and eight month old male patient had recurrent fever for 7 years and his whole body was covered with patchy red rash which was itchy and faded with pressure. The limbs and joints were normal. The levels of high-sensitivity C-reactive protein, erythrocyte sedimentation rate, rheumatoid factors were increased. The patient had fundus arteriosclerosis, double conjunctival lesions and nerve deafness on both sides. There was no mutation found in NLRP3 gene coding region, but a heterozygous mutation (-2667G>T) had been found in 5 ' untranslated region. Compared with normal control, the mRNA level of NLRP3 increased 4.2 times and the expressions of IL-1βand IL-18 gene increased 2.2 (P=0.002) and 1.2 times (P>0.05). Conclusions The clinical features of CAPS can be recurrent fever, rash, and joint involved. The oph-thalmologic abnormalities and varying degrees of deafness may occur during the progression. The test of NLRP3 gene may help diagnosis.

Objective To explore the clinical features of lissencephaly and the detection ofLISI gene.MethodsThe characteristic of clinical features, laboratory examination and gene detection in one case of lissencephaly was retrospectively analyzed. Meanwhile, the related literatures were reviewed.ResultsA 5-month-old female child diagnosed with epilepsy 20 days ago was hospitalized for convulsive seizure more than 30 times in 3 days. The manifestations were eyes staring, and turning upward, cyanosis of lips and face, froth at the mouth, extremities rigidity and loss of consciousness, and the symptoms can spontaneously remitted in 2-3 minutes. Laboratory examination showed that peripheral blood white cell count was 13.67×109/L, hemoglobin 108 g/L, red blood cell count 3.90×1012/L, lymphocyte 10.26×109/L; maocardial enzyme and hepatic and renal function were normal; blood ammonia was 23 μmol/L and lactic acid 2.11 mmol/L. Long-range video EEG showed highly arrhythmia, and frequent partial epilepsy, and sometimes secondary generalized epilepsy. Head MRI showed lissencephaly. The child was treated with oral administration of Keppra 27 mg/(kg·day), Topiramate 6.5 mg/(kg·day), currently no seizure. The detection ofLIS1 gene found that heterozygous mutation of c.232delG, which lead to protein shift mutation (p.E78NfsX25). No mutation was found in her parents.ConclusionsChild with lissencephaly may combine with epilepsy which may cause by mutation inLIS1 gene. And there was no information about point mutation of c.232delG inLIS1 gene being reported at home and abroad so far.

Objective To investigate the association between single nucleotide polymorphism (SNPs) (rs1053005 and rs744166) and expression level of STAT3 gene and the susceptibility to acute lymphoblastic leukemia (ALL) in Chinese children.Methods A case-control study was performed,and 184 children with ALL and 377 healthy children as controls were recruited.The genotypes of 2 SNPs were detected by using polymerase chain reaction-restriction fragment length polymorphism method.And the expression level of STAT3 gene was detected by using real-time PCR;All the data were analyzed by using SPSS 16.0 software.Results (1) In this study,the genotypes (GG,AG,AA) of rs1053005 had a significant difference between the ALL group and control group (x2 =6.737,P =0.034).Compared with control group,the A allele had a higher frequency in ALL group and A allele was a risk factor(x2 =5.853,P =0.016).But,there was no difference in frequency of genotype rs744166 between the 2 groups (x2 =1.866,P =0.393).(2) There was no significant association between genotypes and risk degree among 3 groups (high risk group,medial risk group and standard risk group) (x2 =0.335,P =0.987).(3) The expression level of STAT3 gene in patients with AA genotype was lower than that of the patients with GG genotype (t =4.758,P =0.009);and compared with patients of the standard risk group,high risk patients had a lower expression level of STAT3 gene (t =5.284,P =0.007).Conclusions The polymorphism of SNP rs1053005 was associated with ALL,with A allele being a risk factor;and the expression level of STAT3 gene maybe associated with the risk degree in ALL patients.

Objective To investigate the clinical features of paroxysmal kinesigenic dyskinesia (PKD) and the mutation features of its pathogenic gene proline-rich transmenbrane protein 2 (PRRT2). Method The clinical manifestations and genetic tests of one case of PKD were retrospectively analyzed, and the related literatures were reviewed. Results A 10 year and 9 month male patient was recruited. The age of dyskinesias onset was 7 year and 6 month. The descriptions of the attacks were abnormal involuntary movements which were induced by sudden voluntary movements and presented with dystonia. The frequency of the attacks was three to ifve times per day with the duration lasting ten to twenty seconds, and there is no loss of consciousness. Treatment with oxcarbazepine is effective. A heterozygous mutation in PRRT2 gene, c.649_650insC (p. 217fs224X), was found by genetic testing, and the mutation was inherited from the patient’s mother who showed no symptom of PKD. Conclusion The onset age of PKD could be in the childhood and adolescence. The attack is provoked by sudden movements and the duration time is short. Treatment with antiepileptic drug is effective. The test of PRRT2 gene may help diagnosis. Mutation c.649_650insC is the hotspot mutation of the gene.

Objective To investigate the clinical features of a patient diagnosed with Jacobsen syndrome (JBS) and Paris-Trousseau syndrome (PTS) using chromosomal microarray analysis. Method A retrospective analysis including the patients' clinical manifestations, laboratory examination and genetic analysis was carried out and related literature were reviewed. Results A 14 month-old girl with global development retardation was reported. The patient can sit but cannot walk independently. The patient also presented hypsicephaly, ocular hypertelorism, palpebral ptosis, flat nasal bridge, sparse eyebrows, and speech delay. Gesell development scale showed that the patient was global development retarded with a development level of 40 weeks. No o bvious abnormality was found in EEG but the MRI showed cerebral white matter abnormality. This patient was also diagnosed with neonatal thrombocytopenia in other hospital. Genomic CNVs were detected in this girl, and a 15.7Mb loss was found in the 11q23.3q25 region that covers JBS and PTS region. Conclusions Patient diagnosed with JBS and PTS often present with craniofacial abnormalities, cerebral white matter abnormality and neonatal thrombocytopenia. Chromosomal microarray analysis can help diagnosis.

Objective To investigate the association of single nucleotide polymorphism (rs2295080) inmTOR gene with the susceptibility to acute leukemia (AL) in Chinese children.Methods A case-control study was performed by recruitment of 180 children with AL and 296 healthy children as controls. The genotype of this SNP was detected using PCR-RFLP. The data were analyzed by SPSS19.0.Results There was a signiifcant difference in genotypes in three groups (ALL, AML and con-trol) (P=0.026). And the SNP was associated with AL, with G allele being higher in AL group than that in controls (OR=1.413, 95%CI: 1.050-1.901,P=0.022). In ALL group, G allele was also higher than that in healthy group (OR=1.456, 95%CI: 1.052-2.015, P=0.023). However, no signiifcant association was observed in AML patients (P=0.302). In addition, ALL patients with GG gen-otype were associated with disease severity compared with patients with TT or GT genotype (OR=2.044, 95%CI: 0.569-7.341). ConclusionThe rs2295080 was associated with ALL, with G allele being a risk factor.

Objective To investigate the association between 2 single nucleotide polymorphisms( SNPs) [rs2243250 in interleukin(IL)- 4 gene and rs1800925 in IL - 13 gene]in Henoch - Schonlein purpura(HSP)and Henoch - Schonlein purpura nephritis(HSPN)in Han Chinese children. The level of IL - 4 and IL - 13 in serum were compared between HSP and HSPN. Methods A case - control study was adopted in this research,and 383 children with HSP or HSPN were recruited in this study,409 normal children served as controls. The genotypes of 2 SNPs were detected by using polymerase chain reaction - restriction fragment length polymorphism(PCR - RFLP),and the serum levels of IL - 4 and IL - 13 in HSP and HSPN patients were detected by using enzyme linked immunosorbent assay (ELISA). All the data were analyzed by SPSS 16. 0 software. Results (1)There was no association(polymorphism of SNP rs2243250 in IL - 4 gene)in HSP group and HSPN group compared with the healthy control group(P ﹥ 0. 05);and the polymorphism of another SNP(rs1800925 in IL - 13 gene)was associated with HSP(P = 0. 037),and the fre-quency of T allele of the study group was higher than that of the healthy control group(P = 0. 027). But there was no difference between the study group(HSP group and HSPN group)and the healthy control group in frequency of TT genotype(P = 0. 132),and there was no association between HSPN group and healthy control group(P = 0. 487);also there was no association between polymorphism of this SNP in HSP group and HSPN group(P = 0. 129).(2)There was an association between polymorphism of IL - 13 gene and IL - 13 level in serum,patients with TT genotype had a higher serum IL - 13 level than any other genotypes(P ﹤ 0. 05),but there was no statistically significant difference in IL - 4 level between TT genotype and other genotypes(P ﹥ 0. 05).(3)There was an association between polymorphism of IL - 13 gene and IL - 13 level in serum patients with HSPN who had a higher level of serum IL - 13 than the patients with HSP( P ﹤ 0. 05),but there was no difference in serum IL - 4 level between HSP group and HSPN group. Conclusions The polymorphism of SNP(rs1800925 in IL - 13 gene)was associated with HSP group,and the poly-morphism of this SNP might affect the level of IL - 13 in serum. The patients with HSPN have a higher level of serum IL -13 than the patients with HSP,and high level of IL -13 may be a risk factor in the progression from HSP to HSPN.

Objective To analyze the clinical features and gene mutation in mthylmalonic acidemia (MMA) accompanied by homocysteinemia (cblC), and review the relevant literatures. Methods The clinical features of 3 cases of MMA diagnosed by gene detection were retrospectively analyzed, and meanwhile the pertinent literatures of pathogenesis of MMA, especially combined with late-onset cblC and its gene detection, were reviewed. Results Patient 1 (26 days old) suffered from intermittent convulsions for 3 days, with isosuccinic acid 175.8 μmol/L, C3/C2 rate 1.363, homocysteine >?65 μmol/L and abnormal EEG. MMACHC gene detection found an exon deficiency (delEXON1), which has not been reported. Patient 2 ( 12 year old) was hospitalized for limb shaking, hyperspasmia and vomiting. His isosuccinic acid level was 334.3 μmol/L, C3/?C2 rate was 0.37, homocysteine >?65 μmol/L, and had abnormal EEG. MMACHC gene detection found the mutations of c.482G?>?A and c.609G?>?A. Patient 3 was hospitalized for intermittent convulsions for 20 days, whose isosuccinic acid, C3/?C2 rate, and homocysteine were increased. MMACHC gene detection found the mutations of c.394C?>?T and c.540del8 and c.540del8 had not been reported. Review of literatures discovered that MMA was combined with epileptic seizure in some patents, which further validate that the mutation in MMACHC gene c.482G?>?A may be related to the late-onset of cblC. Conclusions Gene detection contributes to the diagnosis of MMA; the mutation of MMACHC gene c.482G>A may be related to the late-onset of cblC; delEXON1 and c.540del8 are new mutations which have not been reported.