Kwang-Jen Hsiao

Taipei City Hospital, T’ai-pei, Taipei, Taiwan

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Publications (41)173.69 Total impact

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    ABSTRACT: Propionyl-CoA carboxylase (PCC) is involved in the catabolism of branched chain amino acids, odd-numbered fatty acids, cholesterol, and other metabolites. PCC consists of two subunits, α and β, encoded by the PCCA and PCCB genes, respectively. Mutations in the PCCA or PCCB subunit gene may lead to propionic acidemia. In this study, we performed mutation analysis on ten propionic acidemia patients from eight unrelated and nonconsanguineous families in Taiwan. Two PCCA mutations, c.229C→T (p.R77W) and c.1262A→C (p.Q421P), were identified in a PCCA-deficient patient. Six mutations in the PCCB gene, including c.-4156_183+3713del, c.580T→C (p.S194P), c.838dup (p.L280Pfs*11), c.1301C→T (p.A434V), c.1316A→G (P.Y439C), and c.1534C→T (p.R512C), were identified in seven PCCB-deficient families. The c.-4156_183+3713del mutation is the first known large deletion that affects the PCCB gene functions. Furthermore, the c.1301C→T and c.-4156_183+3713del mutations in the PCCB gene have not been reported previously. Clinical features demonstrated that these two frequent mutations are associated with low enzyme activity and a classic propionic acidemia phenotype.
    Biochemical genetics. 05/2014;
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    ABSTRACT: Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). In this study of the PAH mutation spectrum in the Taiwanese population, 139 alleles were identified including 34 different mutations. The V190G, Q267R and F392I mutations are first reported in this study. The most common mutations, R241C, R408Q and Ex6-96A>G, account for 23.2%, 12.0% and 9.2%, of the mutant alleles, respectively. Haplotype analysis shows that R241C and Ex6-96A>G are exclusively associated with haplotype 4.3 to suggest founder effects. On the other hand, R408Q is found on two distinct haplotypes suggesting recurrent mutations. The spectrum of PAH mutations in Taiwan shows various links to those of other Asian regions, yet remarkable differences exist. Notably, R408Q, E286K and -4173_-407del, accounting for 21% of all mutant alleles in Taiwan, are very rare or are undetected among PKU cohorts of other Asian regions to suggest local founder effects. Moreover, the low homozygosity value of 0.092 hints at a high degree of ethnic heterogeneity within the Taiwanese population. Our study of PAH mutation spectrum and the associated haplotypes is useful for subsequent study on the origin and migration pattern via Taiwan, an island at the historical crossroad of migration of ancient populations.Journal of Human Genetics advance online publication, 9 January 2014; doi:10.1038/jhg.2013.136.
    Journal of Human Genetics 01/2014; · 2.53 Impact Factor
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    ABSTRACT: To establish a hearing screening program with high coverage, low referral rate, high follow-up rate, and early intervention in Taipei City. From September 2009 to December 2010, 85% delivery units in Taipei City, which includes 20 hospitals and 14 obstetrics clinics, were recruited into the screening program in two stages. A total of 15,930 babies were born in these participating hospitals and clinics during the program period. Among these neonates, 15,790 underwent hearing screening test with automatic auditory brainstem response (AABR). The screening was free of charge to the parents. The hearing screening examination was performed 24-36h after birth. The same test was repeated between 36 and 60h of age if the baby failed the first hearing test. The neonate was referred to the diagnostic hospitals for further investigations if he failed the second test. The screening coverage rate was 99.1% (15,790/15,930). The incidence of bilateral moderate to severe and unilateral hearing loss was 1.4 per 1000 (22/15,790) and 1.5 per 1000 (24/15,790), respectively. Four percent (626/15,790) of newborns failed to pass the initial screening test and 1.0% of newborns failed to pass the second screening test. Therefore, 1.0% newborns were referred for diagnostic assessments. The follow-up rate was 94.4% (151/160). Sixty-four percent (14/22) of babies with bilateral hearing loss completed the full diagnostic hearing tests within 3 months of birth. The universal newborn hearing screening program is an adequate program for Taipei City with high coverage, low referral rate, and good follow-up rate. Screening fees covered by third parties, two-stage screening steps with AABR strategy, and the stringent monitoring system proved to be effective. 2b, individual cohort study.
    International journal of pediatric otorhinolaryngology 08/2013; · 0.85 Impact Factor
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    ABSTRACT: The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTPS, gene symbol: PTS) is involved in the second step of the de novo biosynthesis of tetrahydrobiopterin (BH4), which is a vital cofactor of nitric oxide synthases and three types of aromatic amino acid hydroxylases; the latter are important enzymes in the production of neurotransmitters. We conducted a study of PTS mutations in East Asia, including Taiwan, Mainland China, Japan, South Korea, the Philippines, Thailand and Malaysia. A total of 43 mutations were identified, comprising 22 previously reported mutations and 21 new discovered mutations. Among these, the c.155A>G, c.259C>T, c. 272A>G, c.286G>A and c.84-291A>G mutations were the most common PTS mutations in East Asia, while the c.58T>C and c.243G>A mutations were, respectively, specific to Filipinos and Japanese originating from Okinawa. Further studies demonstrated that each of the mutations listed above was in linkage disequilibrium to a specific allele of polymorphic microsatellite marker, D11S1347. These results suggest the presence of founder effects that have affected these frequent mutations in East Asia populations. In this context, D11S1347 should become one of the most reliable polymorphic markers for use in prenatal diagnosis among PTPS deficient families, especially where mutations are yet to be identified.
    Journal of Human Genetics 02/2012; 57(2):145-52. · 2.53 Impact Factor
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    ABSTRACT: Mycoplasma fermentans is a potent human pathogen which has been implicated in several diseases. Notably, its lipid-associated membrane proteins (LAMPs) play a role in immunomodulation and development of infection-associated inflammatory diseases. However, the systematic protein identification of pathogenic M. fermentans has not been reported. From our recent sequencing results of M. fermentans M64 isolated from human respiratory tract, its genome is around 1.1 Mb and encodes 1050 predicted protein-coding genes. In the present study, soluble proteome of M. fermentans was resolved and analyzed using two-dimensional gel electrophoresis. In addition, Triton X-114 extraction was carried out to enrich amphiphilic proteins including putative lipoproteins and membrane proteins. Subsequent mass spectrometric analyses of these proteins had identified a total of 181 M. fermentans ORFs. Further bioinformatics analysis of these ORFs encoding proteins with known or so far unknown orthologues among bacteria revealed that a total of 131 proteins are homologous to known proteins, 11 proteins are conserved hypothetical proteins, and the remaining 39 proteins are likely M. fermentans-specific proteins. Moreover, Triton X-114-enriched fraction was shown to activate NF-kB activity of raw264.7 macrophage and a total of 21 lipoproteins with predicted signal peptide were identified therefrom. Together, our work provides the first proteome reference map of M. fermentans as well as several putative virulence-associated proteins as diagnostic markers or vaccine candidates for further functional study of this human pathogen.
    PLoS ONE 01/2012; 7(4):e35304. · 3.53 Impact Factor
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    ABSTRACT: The mut-type methylmalonic aciduria (MMA, MIM 251000) is caused by a deficiency of mitochondrial methylmalonyl-CoA mutase (MCM, E.C. 5.4.99.2) activity, which results from defects in the MUT gene. To elucidate the mutation spectrum of the MUT gene in Chinese MMA patients, 13 exons of the MUT gene, including untranslated regions, were analyzed by PCR-based sequencing for 42 unrelated Chinese MMA patients. All the 42 patients were found to have at least one MUT mutation. A total of 41 mutations were identified. Of these mutations, 20 were novel ones, including one nonsense mutation (c.103C>T), 12 missense mutations (c.316A>C, c.424A>G, c.494A>G, c.554C>T, c.599T>C, c.919T>C, c.1009T>C, c.1061C>T, c.1141G>A, c.1208G>A, c.1267G>A, and c.1295A>C), one duplication (c.755dupA), three small deletions (c.398_399delGA, c.1046_1058del, and c.1835delG), two mutations that might affect mRNA splicing (c.754-1G>A and c.1084-10A>G), and one major deletion. Among the mutations identified, the c.1280G>A (15.5%), c.729_730insTT (10.7%), c.1106G>A (4.8%), c.1630_1631GG>TA (4.8%), and c.2080C>T (4.8%) accounted for 40% of the diseased alleles. The c.1280G>A and c.729_730insTT mutations were found to be the most frequent mutations in Southern and Northern Chinese, respectively. The results of microsatellite analysis suggest that the spread of c.729_730insTT among the Northern Chinese and of c.1280G>A and c.1630_1631GG>TA among the Southern Chinese may have undergone founder effects. This mutation analysis of the gene responsible for mut-type MMA will help to provide a molecular diagnostic aid for differential diagnosis of MMA and could be applied for carrier detection and prenatal diagnosis among Chinese family at risk of mut-type MMA.
    JIMD reports. 01/2012; 6:55-64.
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    ABSTRACT: Recently, the genomes of two Mycoplasma fermentans strains, namely M64 and JER, have been completely sequenced. Gross comparison indicated that the genome of M64 is significantly bigger than the other strain and the difference is mainly contributed by the repetitive sequences including seven families of simple and complex transposable elements ranging from 973 to 23,778 bps. Analysis of these repeats resulted in the identification of a new distinct family of Integrative Conjugal Elements of M. fermentans, designated as ICEF-III. Using the concept of "reaction connectivity", the metabolic capabilities in M. fermentans manifested by the complete and partial connected biomodules were revealed. A comparison of the reported M. pulmonis, M. arthritidis, M. genitalium, B. subtilis, and E. coli essential genes and the genes predicted from the M64 genome indicated that more than 73% of the Mycoplasmas essential genes are preserved in M. fermentans. Further examination of the highly and partly connected reactions by a novel combinatorial phylogenetic tree, metabolic network, and essential gene analysis indicated that some of the pathways (e.g. purine and pyrimidine metabolisms) with partial connected reactions may be important for the conversions of intermediate metabolites. Taken together, in light of systems and network analyses, the diversity among the Mycoplasma species was manifested on the variations of their limited metabolic abilities during evolution.
    PLoS ONE 01/2012; 7(4):e32940. · 3.53 Impact Factor
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    ABSTRACT: Mycoplasma fermentans is a microorganism commonly found in the genitourinary and respiratory tracts of healthy individuals and AIDS patients. The complete genome of the repetitive-sequence-rich M. fermentans strain M64 is reported here. Comparative genomics analysis revealed dramatic differences in genome size between this strain and the recently completely sequenced JER strain.
    Journal of bacteriology 06/2011; 193(16):4302-3. · 3.94 Impact Factor
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    ABSTRACT: Citrin, encoded by SLC25A13 gene, is a mitochondrial solute transporter with a crucial role in urea, nucleotide and protein synthesis. SLC25A13 mutations cause two phenotypes, adult-onset type II citrullinemia and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This study aimed to develop a high resolution melting (HRM) analysis for SLC25A13 mutation scanning and determine the carrier rate in Taiwan. DNAs from healthy subjects (n=479), and patients with hepatocellular carcinoma (HCC, n=100) and NICCD (n=5) were scanned in exons 6, 9, 11, 16, and 17 and parts of introns of SLC25A13 using HRM analysis. All mutations detected by HRM analysis were further confirmed by TaqMan method and/or direct sequencing. In healthy subjects, seventeen carriers with mutants c.851_854del (n=10), c.1638_1660dup, c.615+5G>A (n=4), and two novel mutants, c.475C>T and c.1658G>A, were detected. The frequency of carriers was about 1/28. In patients with HCC, there were only 2 carriers with c.851_854del mutant. Patients with NICCD (n=5) diagnosed during 2007 and 2008, harbored compound heterozygous mutations c.851_854del/c.1177+1G>A, c.851_854del/c.1638_1660dup (n=2), c.851_854del/c.615+5G>A, and c.1638_1660dup/c.615+5G>A. HRM analysis is a simple, rapid and robust method for detecting SLC25A13 mutations in clinical laboratories. SLC25A13 mutations may not be a major contributor to the pathogenesis of HCC in Taiwan.
    Clinica chimica acta; international journal of clinical chemistry 02/2011; 412(5-6):460-5. · 2.54 Impact Factor
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    ABSTRACT: In Taiwan, during the period March 2000 to June 2009, 1,495,132 neonates were screened for phenylketonuria (PKU) and homocystinuria (HCU), and 1,321,123 neonates were screened for maple syrup urine disease (MSUD), methylmalonic academia (MMA), medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency, isovaleric academia (IVA), and glutaric aciduria type 1 (GA-1) using tandem mass spectrometry (MS/MS). In a pilot study, 592,717 neonates were screened for citrullinemia, 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) and other fatty acid oxidation defects in the MS/MS newborn screening. A total of 170 newborns and four mothers were confirmed to have inborn errors of metabolism. The overall incidence was approximately 1/5,882 (1/6,219 without mothers). The most common inborn errors were defects of phenylalanine metabolism [five classic PKU, 20 mild PKU, 40 mild hyperphenylalaninemia (HPA), and 13 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency]. MSUD was the second most common amino acidopathy and, significantly, most MSUD patients (10/13) belonged to the Austronesian aboriginal tribes of southern Taiwan. The most frequently detected among organic acid disorders was 3-MCC deficiency (14 newborns and four mothers). GA-1 and MMA were the second most common organic acid disorders (13 and 13 newborns, respectively). In fatty acid disorders, five carnitine transport defect (CTD), five short-chain acyl-CoA dehydrogenase deficiency (SCAD), and two medium-chain acyl-CoA dehydrogenase (MCAD) deficiency were confirmed. This is the largest case of MS/MS newborn screening in an East-Asian population to date. We hereby report the incidences and outcomes of metabolic inborn error diseases found in our nationwide MS/MS newborn screening program.
    Journal of Inherited Metabolic Disease 10/2010; 33(Suppl 2):S295-305. · 4.07 Impact Factor
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    ABSTRACT: The cblC type of combined methylmalonic aciduria (MMA) and homocystinuria (HC) is the most common inborn error of vitamin B(12) metabolism and is caused by mutations in the MMACHC gene. To elucidate the spectrum of mutations that causes combined MMA and HC in Chinese patients, the MMACHC gene was sequenced in 79 unrelated Chinese patients. Sequence analysis identified 98.1% of disease alleles and found that all patients had at least one MMACHC mutation. A total of 24 mutations were identified. Out of the 24 mutations identified, 9 were novel ones, including missense mutations (c.365A>T and c.452A>G), nonsense mutations (c.315C>G and c.615C>A), deletions (c.99delA and c.277-3_c.303del30), duplications (c.248dupT and c.626dupT) and an insertion (c.445_446insA). The c.609G>A, c.658_660delAAG, c.482G>A, c.394C>T and c.80A>G mutations were the most common mutations and accounted for 80% of disease alleles. Haplotype analysis suggests that the spread of the c.80A>G, c.609G>A and c.658_660delAAG mutations in Chinese patients were caused by a founder effect. The results indicate that defects occurring in the MMACHC gene are the major cause of this disease in Chinese patients with combined MMA and HC, and direct mutation analysis can therefore be used as a rapid confirmatory diagnosis among these Chinese patients.
    Journal of Human Genetics 09/2010; 55(9):621-6. · 2.53 Impact Factor
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    ABSTRACT: The clinical course of methylmalonic aciduria (MMA) is fulminant in neonates and emergency management is necessary to save lives. It is therefore very important to differentiate affected from unaffected neonates immediately when there are abnormal results regarding MMA in newborn screening. Between January 2002 and December 2008, 598,522 newborns were screened for MMA by 2 neonatal screening centers: the Chinese Foundation of Health and the Taipei Institute of Pathology. A total of 22 newborns were referred to confirmatory medical centers, and 7 were confirmed as having MMA. The initial propionylcarnitine (C3) level, C3/acetylcarnitine (C2) ratio, plasma ammonia, liver function tests, blood pH and bicarbonate were compared between the true-positive and false-positive groups. The C3/C2 ratio and plasma ammonia were markedly higher in the true-positive MMA group (p < 0.0001). Blood gas pH (p = 0.029), bicarbonate (p = 0.019), and aspartate aminotransferase (p = 0.005) also significantly differed between these 2 groups. Referred newborns with elevated plasma C3/C2 ratios > 0.4 or ammonia levels > 200 mg/dL should be highly suspected of having MMA.
    Journal of the Chinese Medical Association 06/2010; 73(6):314-8. · 0.75 Impact Factor
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    ABSTRACT: To investigate OPA1 gene mutations in Chinese patients with autosomal dominant optic atrophy and sporadic optic atrophy. Molecular genetic studies and observational case series. Twenty-four patients from 10 unrelated Chinese pedigrees of autosomal-dominant optic atrophy, 35 isolated cases with bilateral optic atrophy of unknown cause, and 50 unrelated normal controls. Genomic DNA was extracted from peripheral blood leukocytes. All 28 coding exons of the OPA1 gene and flanking intron splice sites were sequenced. Putative mutations were reexamined for segregation in the respective families by direct sequencing. Further characterization of selected splicing site mutations was performed by reverse transcription-polymerase chain reaction (PCR) of each patient's leukocyte mRNA. Direct sequencing of the OPA1 gene. Four OPA1 gene mutations were detected, including 2 splicing site mutations (c.1065+2T>C on intron 10 and c.1212+2insT on intron 12), 1 deletion (c.1776_1778delACT on exon 19), and 1 missense mutation (c.2846 T>C on exon 28). The c.1212+2insT, c.1776_1778delACT, and c.2846T>C mutations were newly identified OPA1 mutations. Reverse transcription (RT)-PCR and direct sequencing revealed that the splicing site mutations on c.1065+2T>C and c.1212+2insT caused skipping of exons 10 and 12, respectively. The c.1776_1778delACT mutation led to a deletion of the Leu amino acid on residue 593. OPA1 mutations were found in 4 of 10 familial cases (40 %) and in 1 of 35 sporadic cases of optic atrophy. OPA1 gene mutations are causative in Chinese autosomal-dominant optic atrophy and sporadic optic atrophy. Screening for OPA1 gene mutations in patients with childhood onset optic atrophy who have no affected relatives is useful in making the diagnosis.
    Ophthalmology 12/2009; 117(2):392-6.e1. · 5.56 Impact Factor
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    ABSTRACT: Information regarding growth hormone (GH) therapy in neonatal patients with methylmalonic academia (MMA) is lacking. We present our experience with GH therapy in neonatal patients with MMA. Four neonatal patients with mut 0 type MMA were identified through newborn screening for elevated propionylcarnitine (C3) levels. GH therapy (0.6 IU/kg/week, subcutaneously) was prescribed for patient 1 after 1 month of admission, and was prescribed for patients 2, 3 and 4 on the 1st day of admission. We evaluated weight, skin erosion, hospital stay, and serum levels of C3 after GH therapy. All of the neonatal patients with MMA displayed obvious weight gain and distinct improvement in skin erosions after GH therapy. The duration of hospital stay for patients 2, 3 and 4 was reduced compared to that of patient 1. However, the metabolic effects of GH therapy on reducing serum levels of C3 seem to be indeterminate. Our clinical findings suggest that GH therapy has potentially beneficial effects on neonatal patients with MMA.
    Journal of the Chinese Medical Association 09/2009; 72(9):462-7. · 0.75 Impact Factor
  • Szu-Hui Chiang, Mei-Ling Fan, Kwang-Jen Hsiao
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    ABSTRACT: The nationwide neonatal screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency in Taiwan was started on 1 July 1987. A network of G6PD referral hospitals distributed all around Taiwan was organised for follow-up, confirmatory testing, medical care and genetic counselling. To assess the reliability of confirmatory and screening tests, an external quality assurance (QA) programme for G6PD assay was developed. Lyophilised quality control (QC) materials and dried blood spots were prepared from erythrocytes and whole blood for confirmatory and screening tests, respectively. The external QA surveys were carried out every 1 to 2 months. The QA results were evaluated and compared to the consensus result and reference value. The test results were submitted through internet by participating laboratories and the summary reports were published on a webpage (http:// www.g6pd.tw) within 2 weeks. Twenty-one referral laboratories in Taiwan and 16 screening laboratories in Germany, Lebanon, Mainland China, Philippines, Thailand, Taiwan, Turkey, and Vietnam have been participating in the QA programme. From 1988 to 2007, 144 QA surveys for confirmatory testing were sent to referral laboratories. Among the 2,622 reports received, 292 (11.1%) were found to be abnormal. Interlaboratory coefficient of variation (CV) for the confirmatory test has reached below 10% in recent years. The significant improvement in interlaboratory CV was found to be correlated with the preventive site visits to the referral laboratories since November 2004. From 1999 to 2007, 52 external QA surveys for the screening test were performed. Among 504 reports received, 97 (19.2%) were found to be abnormal. From the 5040 blood spots tested by the screening laboratories, 95 false negative (1.9%) and 187 false positive (3.7%) results were reported. The external QA programme has been useful for monitoring the performance of the referral hospitals and screening laboratories and helpful for the participating laboratories to improve their test quality.
    Annals of the Academy of Medicine, Singapore 12/2008; 37(12 Suppl):84-4. · 1.36 Impact Factor
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    ABSTRACT: To simultaneously assess the effects of exonic mutations on RNA splicing and protein functions, we report here an intron-inclusive cDNA (Intinc) expression system. As a test model, twenty-four mutations in exon 9 of the phenylalanine hydroxylase (PAH) gene were examined in an Intinc expression plasmid composed of the PAH cDNA with the exon 9 flanked by its authentic introns. When the PAH enzyme activities from the Intinc plasmid-transfected cells were compared to those of a standard cDNA expression system, five mutations resulted in significant relative differences in PAH activities attributed to altered exon 9-inclusive mRNA levels. Two of the mutations affected exon recognition probably through splice site modifications and the remaining three affected experimentally verified exon splicing enhancer (ESE) motifs. The Intinc expression system allows not only a better link between mutation genotype to disease phenotype but also contributes to further understanding of molecular mechanisms of deleterious effects of mutations.
    Biochemical and Biophysical Research Communications 07/2008; 373(4):515-20. · 2.28 Impact Factor
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    ABSTRACT: To report the long-term results of early initiation of treatment of 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. Between 1988 and 2000, 12 newborns with PTPS deficiency who underwent early treatment at our hospital were identified. All patients received tetrahydrobiopterin replacement in a daily dosage between approximately 2 and 4 mg/kg. The dosages of levodopa replacement were 10 to 15 mg/kg/d, which is considerably higher than the typically recommended dosages of less than 7 mg/kg/d for patients aged younger than 2 years and 8 to 10 mg/kg/d for patients aged 2 years or older. Replacement with 5-hydroxytryptophan varied widely among patients. Taipei Veterans General Hospital. Patients Twelve newborns. Treatment with tetrahydrobiopterin, levodopa, and 5-hydroxytryptophan. Main Outcome Measure IQ score. The mean (SD) IQ score of our PTPS-deficient patients was 96.7 (9.7; range 86-119), which is considerably higher than previous reports of other populations of PTPS-deficient patients. All patients reached a normal IQ on high daily dosages of levodopa replacement, without developing apparent long-term levodopa-induced adverse effects. We also observed a correlation between long-term IQ score and genotype, birth weight, and age at initiation of treatment. An effective newborn screening referral program and early initiation of appropriate therapy preserved the IQ scores of PTPS-deficient patients.
    JAMA Neurology 04/2008; 65(3):387-92. · 7.58 Impact Factor
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    ABSTRACT: The mosquito, Armigeres subalbatus, mounts a distinctively robust innate immune response when infected with the nematode Brugia malayi, a causative agent of lymphatic filariasis. In order to mine the transcriptome for new insight into the cascade of events that takes place in response to infection in this mosquito, 6 cDNA libraries were generated from tissues of adult female mosquitoes subjected to immune-response activation treatments that lead to well-characterized responses, and from aging, naïve mosquitoes. Expressed sequence tags (ESTs) from each library were produced, annotated, and subjected to comparative analyses. Six libraries were constructed and used to generate 44,940 expressed sequence tags, of which 38,079 passed quality filters to be included in the annotation project and subsequent analyses. All of these sequences were collapsed into clusters resulting in 8,020 unique sequence clusters or singletons. EST clusters were annotated and curated manually within ASAP (A Systematic Annotation Package for Community Analysis of Genomes) web portal according to BLAST results from comparisons to Genbank, and the Anopheles gambiae and Drosophila melanogaster genome projects. The resulting dataset is the first of its kind for this mosquito vector and provides a basis for future studies of mosquito vectors regarding the cascade of events that occurs in response to infection, and thereby providing insight into vector competence and innate immunity.
    BMC Genomics 02/2007; 8:462. · 4.40 Impact Factor
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    ABSTRACT: 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is the most important type of BH4 deficiency related to hyperphenylalaninemia. PTPS deficiency may not only cause a typical phenylketonuric phenotype, but is also accompanied by various neurological signs and symptoms due to impaired synthesis of catecholamines and serotonin. Reports of the long-term outcomes of these patients, especially after delayed onset of therapy, are few. We reviewed the characteristics of 10 PTPS-deficient patients whose treatment onset with tetrahydrobiopterin, L-DOPA, and hydroxytryptophan had been delayed. The relationships among clinical manifestations, biochemical findings, genotypes, and long-term outcomes were analyzed. We classified eight patients as having severe forms, and two as having moderate forms of PTPS deficiency. Improvements in neurological status and intelligence/developmental quotient (IQ/DQ) were observed in all patients, up to approximately 15 years of follow-up. One patient began walking and talking after 4 years of treatment. In patients with severe disease, the mean initial IQ/DQ was 45.40 +/- 13.94, and the final full-scale intelligence quotient (FIQ) score was 62.8 +/- 13.06 (p = 0.042), with a mean increment of 17.4 +/- 5.27 over 15.86 +/- 4.85 years of follow-up. Two patients with moderately severe disease had FIQ increases from 75 to 77 and from 76 to 80 points, respectively. The administration of neurotransmitters based on clinical response and adverse effects was beneficial in patients whose treatment of PTPS deficiency was delayed. Sustained clinical improvements were observed up to 15 years of follow-up.
    Molecular Genetics and Metabolism 03/2006; 87(2):128-34. · 2.83 Impact Factor
  • Nephrology Dialysis Transplantation 03/2006; 21(2):549-50. · 3.37 Impact Factor

Publication Stats

503 Citations
173.69 Total Impact Points

Institutions

  • 2011–2013
    • Taipei City Hospital
      T’ai-pei, Taipei, Taiwan
  • 1998–2012
    • Taipei Veterans General Hospital
      • • Department of Medical Research and Education
      • • Department of Pediatrics
      • • Department of Ophthalmology
      • • Clinical Biochemistry Laboratory
      Taipei, Taipei, Taiwan
  • 1996–2012
    • National Yang Ming University
      • • Institute of Clinical Medicine
      • • Department of Life Sciences / Institute of Genome Sciences
      • • School of Medicine
      T’ai-pei, Taipei, Taiwan
  • 2009
    • Far Eastern Memorial Hospital
      T’ai-pei, Taipei, Taiwan
  • 2002
    • Buddhist Tzu Chi General Hospital
      T’ai-pei, Taipei, Taiwan