Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Liver transplantation for late-onset ornithine transcarbamylase deficiency: A case report.

BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is an X-linked inherited disorder and characterized by marked elevation of blood ammonia. The goal of treatment is to minimize the neurological damage caused by hyperammonemia. OTCD can be cured by liver transplantation (LT). Post-transplant patients can discontinue anti- hyperammonemia agents and consume a regular diet without the risk of developing hyperammonemia. The neurological damage caused by hyperammonemia is almost irreversible. CASE SUMMARY: An 11.7-year-old boy presented with headache, vomiting, and altered consciousness. The patient was diagnosed with late-onset OTCD. After nitrogen scavenging treatment and a protein-free diet, ammonia levels were reduced to normal on the third day of admission. Nevertheless, the patient remained in a moderate coma. After discussion, LT was performed. Following LT, the patient's blood ammonia and biochemical indicators stabilized in the normal range, he regained consciousness, and his nervous system function significantly recovered. Two months after LT, blood amino acids and urine organic acids were normal, and brain magnetic resonance imaging showed a decrease in subcortical lesions. CONCLUSION: LT can significantly improve partial neurological impairment caused by late-onset OTCD hyperammonemic encephalopathy, and LT can be actively considered when early drug therapy is ineffective.

Protist.guru: A Comparative Transcriptomics Database for Protists.

During the last few decades, the study of microbial ecology has been enabled by molecular and genomic data. DNA sequencing has revealed the surprising extent of microbial diversity and how microbial processes run global ecosystems. However, significant gaps in our understanding of the microbial world remain, and one example is that microbial eukaryotes, or protists, are still largely neglected. To address this gap, we used gene expression data from 17 protist species to create protist.guru: an online database equipped with tools for identifying co-expressed genes, gene families, and co-expression clusters enriched for specific biological functions. Here, we show how our database can be used to reveal genes involved in essential pathways, such as the synthesis of secondary carotenoids in Haematococcus lacustris. We expect protist.guru to serve as a valuable resource for protistologists, as well as a catalyst for discoveries and new insights into the biological processes of microbial eukaryotes. AVAILABILITY: The database and co-expression networks are freely available from http://protist.guru/. The expression matrices and sample annotations are found in the supplementary data.

c.3G>A mutation in the CRYAB gene that causes fatal infantile hypertonic myofibrillar myopathy in the Chinese population.

Infantile hypertonic myofibrillar myopathy is characterized by the rapid development of rigid muscles and respiratory insufficiency soon after birth, with very high mortality. It is extremely rare, and only a few cases having been reported until now. Here we report four Chinese infants with fatal neuromuscular disorders characterized by abdominal and trunk skeletal muscle stiffness and rapid respiratory insufficiency progression. Electromyograms showed increased insertion activities and profuse fibrillation potentials with complex repetitive discharges. Immunohistochemistry staining of muscle biopsies showed accumulations of desmin in the myocytes. Powdery Z-bands with dense granules across sarcomeres were observed in muscle fibers using electron microscopy. All patients carry a homozygous c.3G>A mutation in the CRYAB gene, which resulted in the loss of the initiating methionine and the absence of protein. This study's findings help further understand the disease and highlight a founder mutation in the Chinese population.

The BenBioDen database, a global database for meio-, macro- and megabenthic biomass and densities.

Benthic fauna refers to all fauna that live in or on the seafloor, which researchers typically divide into size classes meiobenthos (32/64 µm-0.5/1 mm), macrobenthos (250 µm-1 cm), and megabenthos (>1 cm). Benthic fauna play important roles in bioturbation activity, mineralization of organic matter, and in marine food webs. Evaluating their role in these ecosystem functions requires knowledge of their global distribution and biomass. We therefore established the BenBioDen database, the largest open-access database for marine benthic biomass and density data compiled so far. In total, it includes 11,792 georeferenced benthic biomass and 51,559 benthic density records from 384 and 600 studies, respectively. We selected all references following the procedure for systematic reviews and meta-analyses, and report biomass records as grams of wet mass, dry mass, or ash-free dry mass, or carbon per m2 and as abundance records as individuals per m2. This database provides a point of reference for future studies on the distribution and biomass of benthic fauna.

[Clinical features of children with lysinuric protein intolerance and SLC7A7 gene mutation: an analysis of 3 cases].

Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by SLC7A7 gene mutation and often involves severe lesions in multiple systems. Lung involvement is frequently seen in children with LPI and such children tend to have a poor prognosis. This article summarizes the clinical manifestations and gene mutation characteristics of three children diagnosed with LPI by SLC7A7 gene analysis. All three children had the manifestations of aversion to protein-rich food after weaning, delayed development, anemia, hepatosplenomegaly, and osteoporosis, as well as an increase in orotic acid in urine. In addition, interstitial pneumonia and diffuse pulmonary interstitial lesions were observed in two children. SLC7A7 gene detection showed three pathogenic mutations in these children, namely c.1387delG(p.V463CfsX56), c.1215G>A(p.W405X) and homozygous c.625+1G>A. After a definite diagnosis was made, all three children were given a low-protein diet and oral administration of citrulline [100 mg/(kg.d)], iron protein succinylate [4 mg/(kg.d)], calcium and zinc gluconates oral solution (10 mL/day) and vitamin D (400 IU/day). In addition, patient 3 was given prednisone acetate (5 mg/day). The children had varying degrees of improvement in symptoms and signs. It is hard to distinguish LPI from urea cycle disorder due to the features of amino acid and organic acid metabolism in LPI, and SLC7A7 gene analysis is the basis for a definite diagnosis of LPI.

Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy.

AIM: To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota (GM), and how ketogenic diet (KD) alters GM. METHODS: A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16S rDNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR, and inter-group comparison was conducted by R software. RESULTS: After being on KD treatment for a week, 64% of epileptic infants showed an obvious improvement, with a 50% decrease in seizure frequency. GM structure in epileptic infants (P1 group) differed dramatically from that in healthy infants (Health group). Proteobacteria, which had accumulated significantly in the P1 group, decreased dramatically after KD treatment (P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group, in which Prevotella and Bifidobacterium also grew in numbers and kept increasing. CONCLUSION: GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.

Clinical features of benign epilepsy of childhood with centrotemporal spikes in chinese children.

This multicenter clinical trial was conducted to examine current practice of benign epilepsy with centrotemporal spikes and especially address the question that in what circumstances 1 antiepileptic drug (AED) should be preferred.Twenty-five medical centers participate in this clinical trial. The general information, clinical information, and treatment status were collected under the guidance of clinicians and then analyzed. Difference between different treatment groups was compared, and usefulness of the most commonly used AEDs was evaluated.A total of 1817 subjects were collected. The average age of the subject was 8.81 years. The average age of onset is 6.85 years (1-14 years). Male-to-female ratio is 1.13:1. A total of 62.9% of the patients are receiving monotherapies, and 10.6% are receiving multidrug therapy. Both age and course of disease of treated rolandic epilepsy (RE) patients are significantly different from those of untreated patients. Bilateral findings on electroencephalography (EEG) are less seen in patients with monotherapy compared with patients with multidrug therapy. Except for 25.4% patients not taking any AEDs, oxcarbazepine (OXC), sodium valproate (VPA), and levetiracetam (LEV) are the most commonly used 3 AEDs. VPA and LEV are commonly used in add-on therapy. OXC and LEV are more effective as monotherapy than VPA.Age of onset of Chinese RE patients is 6.85 years. Bilateral findings on EEG could be a risk factor to require multidrug therapy. In Chinese patients, OXC, VPA, and LEV are most commonly used AEDs as monotherapy and OXC and LEV are more effective than VPA.

The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy.

PURPOSE: The ketogenic diet (KD) is an effective treatment for intractable epilepsy (IE), however the therapeutic mechanism is still unclear. This study was designed to investigate T helper type 17/regulatory T cell (Th17/Treg) levels in children with IE and age-matched healthy controls following KD. METHOD: Circulating levels of Th17/Treg cells were analyzed by flow cytometry. Plasma concentration of interleukin (IL)-17 was measured by cytometric bead array assay. Real-time PCR was performed to measure mRNA levels of mTOR, HIF1α and Th17/Treg associated factors in purified CD4(+)CD25(+) T and CD4(+)CD25(-) T cells. RESULTS: By one-way ANOVA, the proportion of circulating Th17 cells and expression of IL-17A and RORγt were significantly higher (P<.05), while the proportion of circulating Tregs and expression of Foxp3, GITR, CTLA-4 were significantly lower (P<.05) in IE patients than healthy subjects. However, these alternations were reversed following KD (P<.05). In CD4(+)CD25(+) T and CD4(+)CD25(-) T cells mTOR and HIF1α expression were significantly higher in IE patients (P<.05), however KD reduced mTOR and HIF1α expression (P<.05). The plasma IL-17A concentrations were higher in IE patients than controls (P<.05). KD partially reduced IL-17A levels (P<.05). CONCLUSION: Our results suggest that Th17/Treg imbalance is characteristic of childhood IE, and may contribute to IE pathogenesis. KD treatment is able to correct this imbalance, probably via inhabiting the mTOR/HIF-1α signaling pathway.

[Brain injury after induction chemotherapy in children with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the changes in brain injury after the induction chemotherapy in children with acute lymphoblastic leukemia (ALL) by cranial MRI. METHODS: The clinical data and cranial MRI results of 62 children with ALL who were hospitalized from March 2014 to June 2015 were analyzed retrospectively. RESULTS: Before chemotherapy, MRI showed bone marrow infiltration of the skull in 33 patients (53%); the children with WBC<20×10(9)/Lhad a significantly lower incidence rate of bone marrow infiltration of the skull than those with WBC≥20×10(9)/L (16 patients/42% vs 17 patients/71%; P<0.05), and the high-risk group had a significantly higher incidence rate of bone marrow infiltration of the skull than the non-high-risk group (71% vs 44%; P<0.05). Before chemotherapy, there were 4 cases (7%) of brain atrophy, and 2 cases (3%) of abnormal signals in the sensory conduction bundle. MRI reexamination in 28 patients after 3 months of chemotherapy showed 3 new cases (11%) of brain atrophy and 1 aggravated case of brain atrophy. CONCLUSIONS: The children with ALL have bone marrow infiltration of the skull, brain atrophy, and abnormal signals in the sensory conduction bundle before chemotherapy, especially bone marrow infiltration of the skull, and some changes in brain injury disappear after treatment.

Meiofaunal communities in a tropical seagrass bed and adjacent unvegetated sediments with note on sufficient sample size for determining local diversity indices.

BACKGROUND: Seagrass beds are highly diverse and productive marine habitats for many associated organisms in nearshore coastal waters. The differences in abundance, diversity, and community structure of benthic invertebrates between seagrass beds and adjacent unvegetated sediments have been stated, whereas most studies are primarily focused on macrofauna or based on a comparatively long distance, i.e., more than 10 m. The present study is designed to test if the community structures of meiofauna, especially the free-living nematodes, differ between seagrass beds and adjacent unvegetated sediments on a meter scale. RESULTS: There are 21 meiofaunal taxa and 63 nematode genera that have been identified from a tropical seagrass bedof Thalassia hemprichii inLudao, Taiwan. Although the compositions of higher meiofaunal taxa are undistinguished, according to correspondence analysis, the assemblages of nematode genera differ substantially between the seagrass bed and unvegetated sediments. Regarding the nematodes, approximately 50% of genera are restricted to the seagrass bed whereas 6% are restricted to unvegetated sediments, which indicate both habitats possessing distinct infaunas. The number of replicates for reasonable estimation of the local diversity index is calculated by the randomization technique. For local seagrass beds, only a single core is sufficient for reliably estimating meiofaunal diversity, but at least three cores or a sample size of 300 individuals is needed for the nematode community. CONCLUSIONS: Nematode assemblages provide more particular differences between seagrass and unvegetated habitats than meiofaunal communities on small spatial scales. Both seagrass beds and adjacent unvegetated sediments harbor specific meiofaunal communities, and hence, the conservation strategy for seagrass should also consider the peripheral bare area of seagrass beds.

[Alterations of CD4+CXCR5+Tfh cells and its transcription regulatory factors in children with asthma].

OBJECTIVE: To study the alterations of follicular T helper cells (CD4(+)CXCR5(+)Tfh cells, Tfh) on circulating T lymphocytes in children with asthma, and to study the expression of transcription regulatory factors BCL-6 and BLIMP-1 mRNA. METHODS: Sixty-four children with asthma and 25 healthy controls were enrolled in this study. On the basis of the disease, the children with asthma were classified into acute phase group (n=36) and remission phase group (n=28). The flow cytometry was used to detect the proportion of CD4(+)CXCR5(+)Tfh cells on CD4(+)T lymphocytes. Real-time PCR was performed to detect the levels of BCL-6 mRNA and BLIMP-1 mRNA. The double -antibody Sandwich ELISA was used to detect plasma concentrations of total IgE, IL-2, IL-6 and IL-21. RESULTS: The proportion of CD4(+)CXCR5(+)Tfh cells was significantly higher in the acute group than in the control group and the remission group (P<0.05). Transcription levels of BCL-6 mRNA were significantly higher, while the inhibitory factors BLIMP-1 mRNA was significantly lower in the acute group than in the remission group and control group (P<0.05). The plasma concentration of IL-6 in the acute group increased significantly compared with the control group (P<0.05). Plasma concentrations of total IgE and IL-21 increased significantly, in contrast, plasma IL-2 concentration decreased significantly in the acute group, compared with the control group and the remission group (P<0.05). Correlation analysis showed that both IL-21 and IL-6 concentrations were positively correlated with the proportion of CD4(+)CXCR5(+)Tfh cells (r=0.76, r=0.46 respectively; P<0.05), while IL-2 level was negatively correlated with the proportion of Tfh cells (r=-0.68, P<0.05). CONCLUSIONS: The abnormal proportion of CD4(+)CXCR5(+)Tfh cells might be involved in the immunological pathogenesis of acute asthma in children. The increased expression of BCL-6 mRNA and decreased expression of BLIMP-1 mRNA as well as the alterations of plasma total IgE, cytokines IL-2, IL-6 and IL-21 in microenvironment might be account for the increased proportion of CD4(+)CXCR5(+)Tfh cells in children with acute asthma.

[Analysis of clinical features and GCDH gene mutations in four patients with glutaric academia type I].

OBJECTIVE: To review clinical features of four male patients with glutaric academia type I and screen glutaryl-CoA dehydrogenase (GCDH) gene mutations. METHODS: The 4 patients underwent brain computer tomography (CT) and magnetic resonance imaging (MRI) analyses. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing. RESULTS: All patients have manifested macrocephaly, with head circumference measured 50 cm (14 months), 47 cm (9 months), 46 cm (5 months) and 51 cm (14 months), respectively. Imaging analyses also revealed dilation of Sylvian fissure and lateral ventricles, frontotemporal atrophy, subarachnoid space enlargement and cerebellar vermis abnormalities. All patients had elevated glutarylcarnitine (5.8 umol/L, 7.5 umol/L, 8.3 umol/L and 7.9 umol/L, respectively) and high urinary excretion of glutaric acid. Seven mutations were identified among the patients, among which c.146_149del4, IVS6-4_Ex7+4del8, c.508A>G (p.K170E), c.797T>C (p.M266T) and c.420del10 were first discovered. CONCLUSION: Macrocephaly and neurological impairment are the most prominent features of glutaric academia type I. Blood tandem mass spectrometry and urine gas chromatographic mass spectrometry analysis can facilitate the diagnosis. The results can be confirmed by analysis of GCDH gene mutations.

Cutaneous reactions induced by oxcarbazepine in Southern Han Chinese: incidence, features, risk factors and relation to HLA-B alleles.

PURPOSE: Oxcarbazepine (OXC) is a promising alternative for patients who cannot tolerate carbamazepine. Recently, however, it has been reported that OXC-induced cutaneous adverse drug reactions (cADRs) are prevalent and may lead to drug discontinuation. Additionally, these reactions are thought to be associated with HLA-B*1502. This study aims to investigate the incidence, features and risk factors of OXC-cADRs, and to explore their relation to HLA-B alleles in Southern Han Chinese. METHODS: A prospective study was performed to investigate the incidence, features and risk factors of OXC-cADRs, in which 252 new users were recruited. To examine the association between OXC-cADRs and HLA-B alleles, 14 maculopapular eruption (MPE) cases, including 9 additional cases beyond this prospective observation, were genotyped by PCR-SSP and sequencing. Thirty-five OXC-tolerant patients served as controls. RESULTS: Five patients (2.0%) developed an OXC-cADR, and all were mild MPE. History of other AED allergy (p=0.005, OR=121.23) and non-AED allergy (p=0.006, OR=59.92) were significant risk factors for OXC-cADRs in multivariate logistic regression analysis. Only one patient with OXC-MPE was positive for HLA-B*1502; and the frequency of HLA-B*1502 in OXC-MPE did not differ significantly from that in OXC-tolerant controls. Four HLA-B*1302 alleles were detected in OXC-MPE cases, which was significantly different from that in general population of southern Han Chinese (p=0.001, OR=7.83). CONCLUSIONS: The incidence of OXC-induced cADRs was low, and no severe reactions occurred. Patients with a history of allergy are more susceptible to OXC-cADRs. No significant association between HLA-B*1502 and OXC-MPE was found. The associations between OXC-MPE and HLA alleles warrant further studies.

[Utilization of high-resolution melting analysis to screen patients with neonatal intrahepatic cholestasis caused by citrin deficiency].

OBJECTIVE: To assess the feasibility of high-resolution melting (HRM) analysis for screening patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). METHODS: Based on previous studies on SLC25A13 gene in Chinese patients with NICCD, four hotspot mutations (851del4, 1638ins23, IVS6+5G>A and IVS16ins3kb) were selected. Results of the HRM analysis was validated using 50 negative controls and 20 patients with NICCD whose genotypes were confirmed previously by direct sequencing. With the established protocol, 171 suspected patients were enrolled. Samples with abnormal melting curves were further validated by DNA sequencing. RESULTS: HRM analysis can accurately determine the genotypes of all negative controls and patients. The sensitivity and specificity of the technique reached 100% (70/70). The melting curves of samples with the same genotype were highly reproducible. In 171 suspected patients, seven NICCD patients were detected by HRM. Identified mutations have included one case of 851del4 homozygote, one case of IVS6+5G>A heterozygote, 3 cases of 851del4 heterozygotes, one case of [IVS6+5G>A]+[ 851del4] and one case of [1638ins23+IVS16ins3kb]+[1638ins23]. All mutations were subsequently confirmed by DNA sequencing. CONCLUSION: HRM analysis is a convenient, high-throughput and rapid technique for the screening of NICCD patients.

[A multicenter controlled study on aripiprazole treatment for children with Tourette syndrome in China].

OBJECTIVE: To evaluate the efficacy and safety of aripiprazole in the treatment of children with Tourette syndrome. METHOD: A prospective, multi-center, controlled clinical trial was conducted in 195 children aged 5-17 years with Tourette syndrome. The patients were assigned to two groups: aripiprazole group (n=98) and tiapride group (n=97), with the treatment dosage of 5-25 mg/d and 100-500 mg/d, respectively. After 12 weeks treatment, the clinical efficacy was assessed by the Yale Global Tic Severity Scale (YGTSS) score, and adverse reactions were observed by side effects symptoms scale, blood biochemical indexes, and electrocardiography. RESULT: Significant pre- and post-treatment differences were ascertained for motor tic, phonic tic, function damage and total scores of YGTSS in the both groups from the second week of treatment (P<0.0001). Compared with the tiapride group, the aripiprazole group showed a more significantly decreased function damage score of YGTSS by the second week of treatment (P<0.05). After 12 weeks treatment, total scores of YGTSS in the aripiprazole group decreased from 53.74±15.71 at baseline to 24.36±16.38, while in the tiapride group from 51.66±13.63 to 23.26±15.31. The mean reduction scores of YGTSS were 29.38 in the aripiprazole group and 28.40 in the tiapride group at the end of treatment, and the clinical response rates were 60.21% and 63.92%, respectively. There were no significant differences between the 2 groups (P>0.05). The incidence of adverse reactions was similar in the aripiprazole and tiapride groups, with 29.6% and 27.8% respectively. There were no significant differences in the incidence of adverse reactions between aripiprazole and tiapride groups and no severe adverse events were found in either group. CONCLUSION: The results showed that aripiprazole showed similar therapeutic effect to tiapride in treatment of children with Tourette syndrome. Aripiprazole was safe and well tolerated in Chinese population, and can be considered as a new valid option for the treatment of tic disorders.

[SLC25A13 gene analysis in neonates with intrahepatic cholestasis caused by citrin deficiency].

OBJECTIVE: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) which resulted from mutation in SLC25A13 gene can present transient intrahepatic cholestasis, low birth weight, growth retardation, hypoproteinemia and so on. This study aimed to identify the mutation type of NICCD patients by DNA sequencing. METHODS: Twenty children diagnosed as NICCD were consented to enroll in this study. PCR assays were performed to amplify the eighteen exons and its flanking sequences of SLC25A13 gene, which were defined as the upstream and downstream 50 bp from starting and ending site of the exons. Then the PCR products were purified and followed by automated DNA sequencing. The IVS16ins3kb mutation was detected by nested PCR and RT-PCR. RESULTS: Seven genetic variations of SLC25A13, termed as 851del4, 1638ins23, IVS16ins3kb, IVS6+5G>A, c.775C>T (p.Q259X), c.1505C>T (p.P502L) and c.1311C>T (p.C437C), were identified in the subjects, of which c.775C>T (p.Q259X), c.1505C>T (p.P502L) and c.1311C>T (p.C437C) were reported for the first time in NICCD patients. And a compound mutation ofï¼»1638ins23+IVS16ins3kbï¼½was also identified. In 20 patients with NICCD, 6 patients were 851del4 homozygotes, 7 patients were compound heterozygotes, and 7 patients were heterozygotes of single mutation. 851del4 was the major mutation type (64%), followed by 1638ins23 (15%), IVS16ins3kb (12%) and IVS6+5G>A (6%). CONCLUSIONS: 851del4 is the major mutation type in Chinese patients with NICCD.

[Analysis of clinical features and gene mutations in two Chinese pedigrees with late-onset methylmalonic acidemia, cblC type].

OBJECTIVE: CblC is the most common type of methylmalonic acidemia with homocysteinemia. MMACHC is the coding gene. This study aimed at understanding clinical features and gene mutations in 2 Chinese pedigrees who had late-onset methylmalonic acidemia complicated with homocysteinemia. METHOD: The clinical data of 2 cases were analyzed. The MMACHC gene mutation was detected using polymerase chain reaction (PCR) and DNA sequencing. RESULT: The age of onset was 13 years and 12 years, respectively. They both presented with nervous system symptoms. The main clinical features were developmental retardation and degradation, including motion, speech and intelligence. One patient complained of anemia. The other patient was misdiagnosed as having a viral encephalitis. Both patients showed remarkable elevation of methylmalonic acid and homocysteine levels in urine. Both had received therapy with vitamin B(12). The symptoms were rapidly relieved. The follow-up till now showed apparent improvement in the 2 cases. Three mutations in the MMACHC gene were found in the two Chinese pedigrees. Both patients were compound heterozygotes of two mutant alleles: one patient had a G-to-A transition at nucleotide 482 (G482A) that caused an arginine-to-glutamine substitution at position 161 of the protein (R161Q), and a deletion of AAG at nucleotide 658_660 (658_660delAAG) which resulted in lysine deleting at position 220 of the protein (K220del); the other patient had a G482A and a G-to-A transition at nucleotide 609 (G609A) that caused a tryptophan-to-termination codon substitution at position 203 of the protein (W203X). Otherwise, the authors also detected parents of two families. Each had a heterozygote of one mutation. CONCLUSION: Late-onset methylmalonic acidemia patients had a variety of clinical manifestation, the first symptom was mainly abnormality of nervous system. One case was accompanied with hematological abnormalities. Two patients were vitamin B(12) responsive. In this study, the mutations were all detected on the fourth exon, the G482A mutation was probably associated with late-onset cases.