Biomedical subjects

Y J Jong

Publications and source records attributed to Y J Jong.

At least 19 recordsLinked to original sources

PubMed2001

No association of the dopamine transporter gene 3' VNTR polymorphism with ADHD subtypes in a population sample of twins.

Dopamine pathway genes have been the subject of a variety of studies testing the association of candidate genes and liability for attention-deficit hyperactivity disorder (ADHD). Due to the known effects of stimulant medications such as methylphenidate on the dopamine transporter, a variety of case control and family-based transmission distortion genetic studies of ADHD have focused on DAT1 polymorphisms. The most widely reported positive finding has been with a variable number of tandem repeats (VNTR) polymorphism of unknown function in the 3' untranslated region of the DAT1 gene. In this report, we test for association of alleles of this polymorphism with ADHD using population-derived samples of twins. We use the transmission disequilibrium test and ADHD subtypes defined by both DSM-IV and latent class criteria. We fail to demonstrate any significant association or trend for association of any of the VNTR alleles with any of the variously defined ADHD subtypes.

Adolescent↗

PubMed2001

Molecular analysis of SMN, NAIP and P44 genes of SMA patients and their families.

Mutations of the telomeric survival motor neuron gene (SMN1) are related to spinal muscular atrophy (SMA). However, no phenotype-genotype correlation has been observed since the SMN1 gene is lacking in the majority of patients affected with either the severe form (type I) or the milder forms (types II and III). Here, we analyze the SMN, NAIP and P44 genes in 132 Chinese SMA patients and their families. At least three types of normal allele, and four types of mutant allele were found in this study. The combination of one normal allele with one mutant allele resulted in carriers of different types, and the combination of different mutant alleles accounted for the different genotypes among different types of SMA. Deletions of mutant alleles can be further subgrouped into four types, which includes involving SMN1, SMN1 and NAIP(T) (telomeric portion of NAIP gene), SMN1 and NAIP(T) and P44(T) (telomeric portion of P44 gene), and SMN1 and SMN2 (centromeric portion of SMN gene). Some of the severe (type I) SMA cases correlated with the extent of deletions in the SMN, NAIP and P44 genes or the dosage of SMN gene when both SMN1 and SMN2 are deleted. We also found two novel point mutations, an A insertion at codon 8 (AGT-->AAGT) and an A substitution at codon 228 (TTA-->TAA).

Anterior Horn Cells↗

PubMed2001

Treatment of spinal muscular atrophy by sodium butyrate.

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular paralysis with muscular atrophy. No effective treatment of this disorder is presently available. Studies of the correlation between disease severity and the amount of survival motor neuron (SMN) protein have shown an inverse relationship. We report that sodium butyrate effectively increases the amount of exon 7-containing SMN protein in SMA lymphoid cell lines by changing the alternative splicing pattern of exon 7 in the SMN2 gene. In vivo, sodium butyrate treatment of SMA-like mice resulted in increased expression of SMN protein in motor neurons of the spinal cord and resulted in significant improvement of SMA clinical symptoms. Oral administration of sodium butyrate to intercrosses of heterozygous pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all three types of SMA-like mice. These results suggest that sodium butyrate may be an effective drug for the treatment of human SMA patients.

Abnormalities, Multiple↗

PubMed2001

Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes in a population sample of twins.

Attention-deficit hyperactivity disorder (ADHD) is a common, highly heritable syndrome of childhood characterized by problems with inattention, hyperactivity, and impulsivity. A variety of case control and family-based transmission distortion genetic studies of ADHD have focused on the possible involvement of polymorphisms of the DRD4 receptor gene. The majority of studies have examined the association of variously defined ADHD with an exon 3 polymorphism containing a variable number of imperfect 48 base pair repeats. Recently, McCracken et al. [2000: Mol Psych 5:531-536] reported an association of the DSM-IV primarily inattentive ADHD subtype with a 5' 120 base pair repeat polymorphism in the DRD4 gene. In this report, we test for the possible association of these two polymorphisms with population-derived samples of DSM-IV ADHD subtypes. Furthermore, we extend previous studies by testing for associations with ADHD subtypes derived from latent-class analysis of interview responses. In contrast to most, but not all, previous studies, we failed to demonstrate any significant association of the exon 3 7-repeat allele with ADHD. Nor did we replicate the association of the 5'120 base pair repeat polymorphism. We do find a significant association of the exon 3 3-repeat allele with a novel talkative/impulsive latent-class-defined subtype of ADHD.

Adolescent↗

PubMed2001

An effective strategy of using molecular testing to screen mentally retarded individuals for fragile X syndrome.

Fragile X syndrome (FXS) is the most common form of familial mental retardation (MR). It is caused by the expansion of the CGG repeat in the FMR1 gene on the X chromosome. To date, FXS is not treatable, but can be prevented by prenatal genetic examination. Identifying women who carry a full mutation or premutation FMR1 gene is thus very important, and can be done by tracing family members of FXS subjects. However, most of the FXS subjects in Taiwan as well as those in many other countries have not been identified. In this study the authors attempt to develop reliable and inexpensive tests suitable for a large-scale screen of subjects with MR for FXS. Together with their previous study, a total of 311 male and 160 female subjects with MR were screened with nonradioactive Southern blot assay using mixed deoxyribonucleic acid from three subjects of the same sex. From these subjects, nine male subjects and one female FXS subject were diagnosed. All male subjects were also screened with nonradioactive polymerase chain reaction (PCR). These nine male FXS subjects were also detected on the basis of PCR amplification failure. No false-negative results were discerned. The PCR procedure was simplified further by combining it with an analysis of a blood spot on filter paper, which is a much simpler and cheaper method for sample collection and DNA preparation. This method was then used to screen 104 boys with MR. Two of them were suspected, and later confirmed with Southern blot assay, as subjects with FXS. This study suggests that simple PCR combined with blood spot analysis could be a reliable, inexpensive test that is feasible for a large-scale screening of male subjects with MR for FXS. However, Southern blot assay with mixed deoxyribonucleic acid is appropriate for screening female subjects. Based on this strategy, most FXS subjects could be identified easily for further management.

Blotting, Southern↗

PubMed2001

Superior mesenteric artery syndrome associated with hereditary motor and sensory neuropathy type II--a case report.

A 14-year-old girl with superior mesenteric artery (SMA) syndrome associated with hereditary motor and sensory neuropathy (HMSN) type II is reported. The initial presentations of HMSN type II were developmental delay and gait disturbance at 2 years of age. All deep tendon reflexes were absent. Nerve conduction velocities and left sural nerve biopsy all revealed axonal changes. Recently, she suffered from intermittent bilious vomiting and epigastralgia for 6 months. That caused body weight loss from 40 kg to 28 kg. Abdominal echography showed narrowed superior mesenteric artery angle. Upper gastrointestinal series revealed obstruction of third portion of duodenum. Accordingly, SMA syndrome was diagnosed. To the best of our knowledge, this case is the first report of SMA with HMSN type II in the world. When a child with chronic neurological disease presents with intermittent vomiting, SMA should be considered as a disease entity of differential diagnosis.

Adolescent↗

PubMed2000

Analysis of the mRNA transcripts of the survival motor neuron (SMN) gene in the tissue of an SMA fetus and the peripheral blood mononuclear cells of normals, carriers and SMA patients.

Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of the anterior horn cells of the spinal cord. The gene most highly associated with SMA is the survival motor neuron (SMN) gene. In this study, we present an analysis of messenger RNA (mRNA) expression of the SMN gene in peripheral blood mononuclear cells in normal subjects, SMA carriers and patients from 20 SMA families. We found at least 6-8 different transcripts of SMN gene formed by alternative splicing involving exons 3, 5 and 7. We compared transcripts from the different types of SMA and found no definite differences in transcript patterns and amounts. Normal subjects with the telomeric SMN (SMN(T)) gene only had variable splicing resulting in several transcripts, the most dominant being a transcript containing all coding regions. However, SMA patients with the centromeric SMN (SMN(C)) gene only had a higher degree of splice variation and tended to show little or no exon 7. These results demonstrate that SMN(T) and SMN(C) genes participate in alternative splicing phenomena. The different splicing patterns support the view that the SMN(T) gene is responsible for SMA disease. We also analyzed the transcripts from several tissues of an SMA fetus who had a homozygous SMN(T) gene deletion. Different splicing patterns were also found in these tissues, and were similar to the splicing pattern of leukocytes. We compared the major transcripts from exons 4 to 8 of both the SMN(T) and SMN(C) genes and found that the relative proportion varied among normal subjects, SMA carriers and patients. This approach could be used as a novel diagnostic method. We suggest that analyzing the mRNA expression of the SMN gene in peripheral blood mononuclear cells offers an apparently reliable technique for separating SMA patients, carriers, and normal individuals.

Adult↗

PubMed2000

Genetic heterogeneity in three Chinese children with Fukuyama congenital muscular dystrophy.

Three Chinese patients, two boys and one girl, were afflicted with the typical clinical, myopathological and neuroradiological findings of Fukuyama congenital muscular dystrophy (FCMD). Polymorphism analysis of our patients did not reveal the founder haplotype (138-192-147-183 in D9S2105-D9S2170-D9S2171-D9S2107) of Japanese FCMD, even though one patient was descended from Japanese ancestry. Full mutational analysis of the fukutin gene revealed that there is neither 3 kb insertion nor point mutation. These findings suggest genetic heterogeneity between Chinese and Japanese FCMD patients.

Child↗

PubMed2000

A mouse model for spinal muscular atrophy.

The survival motor neuron gene is present in humans in a telomeric copy, SMN1, and several centromeric copies, SMN2. Homozygous mutation of SMN1 is associated with proximal spinal muscular atrophy (SMA), a severe motor neuron disease characterized by early childhood onset of progressive muscle weakness. To understand the functional role of SMN1 in SMA, we produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2. Smn-/- mice died during the peri-implantation stage. In contrast, transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathological changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. Our results demonstrate that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn-/-SMN2 mice reflect those seen in SMA patients, providing a mouse model for this disease.

Animals↗

PubMed2000

Analysis of an SMN gene-like DNA fragment.

Part of a survival motor neuron (SMN) gene-like DNA fragment has been identified. This DNA fragment was accidentally isolated from cDNA by RT-PCR using primers specific for the region between exon 3 and 6 of the SMN gene. This fragment was used as a probe to hybridize the mRNA from several tissues, but we have been unable to detect any transcript of this SMN-like gene in these tissues. Thus, we have inferred this SMN gene-like fragment was a genomic product contaminant that was amplified in the reaction. Sequencing analysis of this fragment, which contains several stop codons, revealed a 74.6% nucleotide homology with the SMN gene. From these results, we believe that this DNA fragment is not a mutated form of SMN gene. Rather, it is an SMN-like pseudogene, which is variably present even in normal individuals.

Base Sequence↗

PubMed2000

Applicability of BSID-II in diagnosing developmental delay at Kaohsiung area.

The purpose of this study was to investigate the applicability of BSID-II in diagnosing children with developmental delay in Kaohsuing area. Five hundred and forty-four children, all who were patients of Developmental Delay Clinic of Kaohsuing Medical University, participated in this study. The instrument of this study was the Bayley Scales of Infant Development--second edition (BSID-II), the primary value of which was in diagnosing developmental delay and planning intervention strategies. The standardization and statistical properties of BSID-II made it one of the best measures of infant development available. The findings as follows: (1) the alpha coefficients were between .95 and .99, which were higher than data on manual of BSID-II; (2) the reproducibilities, which were different with each examiner, were between .9503 and .9633, that were good enough to be a developmental scale; (3) Standard Errors of Measurement were between 2.8589 and 3.8206. It was a restricted sample so that these also were lower than the data on manual of BSID-II. This evidence shows BSID-II is a highly reliable instrument of developmental assessment at Kaohsuing area. A special norm for developmentally delayed children and quality control of examiners are suggested.

Child, Preschool↗

PubMed2000

Parents' psychosocial problems influencing the continuity of early intervention treatment in children with developmental delay.

Developmental delay is a chronic disorder, which has a significant and continuing impact on the developmental progress of children. Whether the developmentally delayed children have continuous early intervention treatment is important for the success of early intervention. Professionals in early intervention services have been encouraged to understand parents' psychosocial problems and to further enhance their understanding of care for their delayed children. The purposes of this study were two-fold. The first was to identify the parents' psychosocial problems. The second purpose was to find parents' psychosocial variables that could be used to significantly discriminate whether the retarded children have continuously received treatment programs. A questionnaire to investigate parents' psychosocial problems was implemented. It mainly consisted of twenty descriptive items concerning parents' psychosocial conditions. Parents used a four-point Likert scale to rate the likelihood of the items. Parents also responded as to whether their child had received treatments continuously. Subjects were the parents of children who were diagnosed to have developmental delay. Factor analysis and discriminant analysis was used for statistical data examination. Analyzed data were from 207 completely finished questionnaires. Six parents' psychosocial factors were extracted via factor analysis, and they accounted for 46.9% of the variance of the twenty items. The factors were identified as family income, family members' relationships, caring skills, supporting resources, acceptance of the retarded child, and self-psychological adaptation. About half of the children had received treatment continuously. Discriminant analysis revealed that family income was crucial to parents' capacity to meet the needs for treatment.

Adult↗

PubMed1999

Prenatal prediction of spinal muscular atrophy in Chinese.

We used linkage analysis, non-isotope SSCP (single-strand conformation polymorphism) and PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) for prenatal diagnosis of spinal muscular atrophy (SMA). A total of 26 cases from 20 SMA families (16, type 1 and 4) were evaluated. 5 out of 26 fetuses were affected and, following genetic counselling, the parents decided to terminate the pregnancies. Aborted fetal tissues were examined and the diagnosis was confirmed in each case. The 21 unaffected cases were either normals (12 cases) or carriers (9 cases). These children have been followed for six months to two and a half years. No false-negative or false-positive results on prenatal testing were found. We conclude that prenatal diagnosis of SMA is reliable and accurate.

Deoxyribonucleases, Type II Site-Specific↗

PubMed1999

Growing skull fractures.

Growing skull fractures are rare complications of severe closed head injury occurring almost exclusively in infants and children under the age of three. The reported incidence is between 0.05% and 0.6%. Two such cases were treated at our institution. Both cases presented with bulging mass and underlying skull defect two months after head injury. They received surgical treatment and achieved excellent results. Early diagnosis and surgical intervention are essential for these patients to prevent progressive brain damage. Therefore, close follow-up for patients at risk of developing growing skull fracture is necessary.

Craniocerebral Trauma↗

PubMed1998

Preparation and characterization of heparin-containing SBS-g-DMAEMA copolymer membrane.

The grafting of dimethyl amino ethyl methacrylate (DMAEMA) onto styrene-butadiene-styrene triblock copolymer (SBS) membrane was subsequently conducted by UV-radiation induced graft copolymerization without degassing to obtain the SBS-g-DMAEMA copolymer membrane. The substituted amino groups on the SBS-g-DMAEMA graft copolymer membrane were quaternized with iodomethane, and then the membrane was treated with heparin to prepare the heparin-containing SBS-g-DMAEMA copolymer membrane (SBS-g-DMAEMA-HEP). The graft copolymer membrane (SBS-g-DMAEMA) and the heparin-containing SBS-g-DMAEMA copolymer membrane (SBS-g-DMAEMA-HEP) were characterized by FTIR spectroscopy. The heparin content was determined by toluidine blue heparin assay. Contact angle, water content, and protein adsorption of fibrinogen and albumin experiments were also performed to evaluate the effect of graft amount and heparin content on the biocompatibility of SBS-g-DMAEMA and SBS-g-DMAEMA-HEP graft copolymer membranes. By using Kaelble's equation, the surface tension of SBS-g-DMAEMA and SBS-g-DMAEMA-HEP were determined. It was found that with increasing grafting amount and the heparin content, the surface tension and water content of SBS-g-DMAEMA membrane increased, whereas the contact angle decreased. The amount of the adsorption of albumin and fibrinogen decreased with increasing graft amount and heparin content. However, there was a minimum for adsorption of proteins in the SBS-g-DMAEMA and SBS-g-DMAEMA-HEP membranes.

Biocompatible Materials↗

PubMed1998

Mutation analysis of Wilson disease in Taiwan and description of six new mutations.

Wilson disease is an autosomal recessive disorder of copper metabolism. Mutation screening in Wilson disease has led to the detection of at least 89 disease-specific mutations. Some mutations appear to be population specific, while others are common to many populations. In this study, 38 Taiwanese patients with Wilson disease were screened using single-strand conformation polymorphism analysis, followed by direct DNA sequencing. We found 12 different mutations, six of which were novel. All our detected mutations were found to be in eight exons. Four mutations in three loci (Arg778Gln, Arg778Leu, Gly943Asp, and Pro992Leu) accounted for about 58% of the mutant alleles we detected. Using an RNA transcriptional assay, we confirmed that both of our detected splice-site mutations resulted in exon skipping.

Alleles↗

PubMed1998

Large-scale deletions in a Chinese infant associated with a variant form of Werdnig-Hoffmann disease.

A Chinese male infant with arthrogryposis multiplex congenita (AMC), ventricular and atrial septal defects, and Werdnig-Hoffmann disease (WHD) had deletions of the telomeric copy of the survival motor neuron (SMN(T)) and neuronal apoptosis inhibitory protein genes. Children with AMC or congenital heart disease, or both, and motor neuron disease should undergo testing for SMN(T) deletion. This rare association further illustrates the variable phenotypic expressions of WHD.

Arthrogryposis↗

PubMed1998

Rapid detection of a recombinant hotspot associated with Charcot-Marie-Tooth disease type IA duplication by a PCR-based DNA test.

A 1.5-Mb duplication on chromosome 17p11.2-p12 (CMT1A duplication) caused by a misalignment of the CMT1A repeat sequences (CMT1A-REPs) is associated with Charcot-Marie-Tooth disease type 1A (CMT1A). A hotspot of crossover breakpoints located in a 3.2-kb region of the CMT1A-REPs accounts for three-quarters of the rearrangements in CMT1A patients. We developed a PCR-based diagnostic method to detect a recombination hotspot associated with the CMT1A duplication. Thirty-one CMT1A Chinese patients from different families and 50 healthy people over 65 years of age were studied. Twenty-seven of the 31 cases demonstrated the 3.2-kb hotspot crossover, of which there were two subgroups. The type 1 crossover breakpoint was located at the distal CMT1A-REP around the PmeI site, and accounted for 24 of the 27 cases with a 3.2-kb hotspot crossover in CMT1A duplication patients. The type 2 crossover breakpoint was located at the distal CMT1A-REP around the base 3625 region, accounting for 3 of the 27 cases. The results correlated very well with the results of Southern transfer analysis. This study has a potentially important role in the diagnosis of CMT1A disease.

Charcot-Marie-Tooth Disease↗