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Biomedical subjects

S H Hahn

Publications and source records attributed to S H Hahn.

At least 19 recordsLinked to original sources
PubMed2006

Stabilization of hypoglycosylation in a patient with congenital disorder of glycosylation type Ia.

A follow-up over 7 years on a patient with congenital disorder of glycosylation type Ia showed a significant normalization of hypoglycosylated transferrin. Isoelectric focusing for serum transferrin is a widely used screening method but there could be a limit of detection and the subtle changes can be also overlooked. Re-test with a different method is desirable, especially when the clinical suspicion for congenital disorder of glycosylation is high.

Carbohydrate Metabolism, Inborn Errors↗
PubMed2004

The urinary excretion of glutarylcarnitine is an informative tool in the biochemical diagnosis of glutaric acidemia type I.

Glutaric acidemia type I (GA-1) is a progressive neurodegenerative inborn error of metabolism that typically manifests acutely in infants during an intercurrent illness. The diagnosis is established biochemically by the detection of glutaric acid and 3-hydroxy glutaric acid in urine and glutarylcarnitine in plasma. However, some patients excrete only small amounts of glutaric acid and may be overlooked, especially if the plasma concentration of glutarylcarnitine is not elevated. To test the hypothesis that measuring the excretion of glutarylcarnitine may improve the recognition of GA-1 patients without significant glutaric aciduria, urine glutarylcarnitine was analyzed in 14 cases. Five of them lacked significant glutaric aciduria, 9 (of 10 available) had a normal plasma glutarylcarnitine concentration. As controls, we also evaluated 54 subjects with glutaric aciduria secondary to other causes (16-7509 mmol/mol creatinine; reference range: <15; no significant amounts of 3-hydroxy glutaric acid detectable). The excretion of glutarylcarnitine was significantly elevated in all GA-1 patients (14-522 mmol/mol creatinine; reference range: <5.2) and in none of the controls with glutaric aciduria. These findings suggest that the urinary excretion of glutarylcarnitine is a specific biochemical marker of GA-1 which could be particularly useful in the work up of patients with suggestive clinical manifestations but without glutaric aciduria and with normal plasma acylcarnitine profiles.

Carnitine↗
PubMed2004

A novel splice acceptor mutation in the DSPP gene causing dentinogenesis imperfecta type II.

The dentin sialophosphoprotein (DSPP) gene (4q21.3) encodes two major noncollagenous dentin matrix proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Defects in the human gene encoding DSPP cause inherited dentin defects, and these defects can be associated with bilateral progressive high-frequency sensorineural hearing loss. Clinically, five different patterns of inherited dentin defects are distinguished and are classified as dentinogenesis imperfecta (DGI) types I, II, and III, and dentin dysplasia types I and II. The genetic basis for this clinical heterogeneity is unknown. Among the 11 members recruited from the studied kindred, five were affected with autosomal dominant DGI type II. The mutation (g.1188C-->G, IVS2-3C-->G) lay in the third from the last nucleotide of intron 2 and changed its sequence from CAG to GAG. The mutation was correlated with the affection status and was absent in 104 unaffected individuals (208 alleles) with the same ethnic and geological background. The proband was in the primary dentition stage and presented with multiple pulp exposures. The occlusal surface of his dental enamel was generally abraded, and the dentin was heavily worn and uniformly shaded brown. The dental pulp chambers appeared originally to be within normal limits without any sign of obliteration, but over time (by age 4), the pulp chambers became partially or completely obliterated. The oldest affected member (age 59) showed mild hearing loss at high-frequency (8 kHz). Permanent dentition was severely affected in the adults, who had advanced dental attrition, premature loss of teeth, and extensive dental reconstruction.

Adolescent↗
PubMed2004

Rapid, comprehensive screening of the human medium chain acyl-CoA dehydrogenase gene.

Newborn screening by tandem mass spectrometry (MS/MS) identifies patients with medium chain acyl-CoA dehydrogenase (MCAD) deficiency the most frequently observed disorder of fatty acid oxidation. Molecular genetic analysis is becoming a common tool to confirm those identified as affected by prospective screening and for carrier detection in family studies. The A985G (K304E) mutation accounts for approximately 80% of mutant alleles in MCAD deficient patients, presenting symptomatically, while greater variability of mutant alleles is observed among cases identified through prospective screening. Aside from A985G, the mutation spectrum in MCAD deficient patients is heterogeneous such that comprehensive gene analysis is required. Traditionally the MCAD gene is assayed by sequencing the entire coding region. Although effective and definitive, this approach is expensive, turn around time is slow, and is poorly amenable to a clinical service molecular genetics laboratory. Dye-binding/high-resolution thermal denaturation is a rapid and homogeneous method by which to scan a PCR product for evidence of sequence aberration. PCR is performed in capillaries in the presence of the dsDNA-binding dye LCGreen I and subsequently the DNA/dye complexes are analyzed by high-resolution thermal denaturation. DNA sequencing was limited to fragments displaying abnormal melting profiles. Of 18 specimens analyzed, 11 have a genotype consistent with MCAD deficiency and seven have a genotype consistent with carrier status. Clinical and biochemical data corroborate that the genotype results identified the affected patients and differentiates them from carriers. The entire process is homogeneous requiring no post-PCR manipulation and is completed in under 3 h.

Acyl-CoA Dehydrogenase↗
PubMed2003

Mutation analysis of copper transporter genes in patients with ethylmalonic encephalopathy, mitochondriopathies and copper deficiency phenotypes.

The trace metal copper is an essential cofactor for a number of biological processes, including mitochondrial oxidative phosphorylation, free-radical eradication, neurotransmitter synthesis and maturation, and iron metabolism. Consequently, copper transport at the cell surface and the delivery of copper to intracellular proteins are critical events in normal cellular homeostasis. Four genes have been reported to influence the cellular uptake and the delivery of copper to specific cell compartments and proteins. These include hCTR1, which regulates cellular copper uptake; HAH1, which mediates the transfer of copper to the Menkes and Wilson disease transporters; CCS, which is related to the transfer of copper to superoxide dismutase; and hCOX17, which directs trafficking of copper to mitochondrial cytochrome-c oxidase. At present, no genetic disorders have been associated with defects in these four copper transporter genes. In this study, we test the possibility that defective copper uptake or intracellular translocation represents the basic defect in three categories of candidate phenotypes among 22 patients: ethylmalonic encephalopathy; mitochondriopathies of unknown aetiology; and neurodevelopmental abnormalities with clinical and chemical evidence of copper deficiency. Mutation analyses of the copper uptake protein, hCTR1, and the three copper chaperones were performed by direct sequencing of the whole coding regions. No causative mutations were identified for the four copper transporter genes in 22 patients. A heterozygous polymorphism (847G>A) for CCS was detected in 7 patients. For the distinct disease entity ethylmalonic encephalopathy, we additionally show normal mRNA levels for each of the four genes. The negative results notwithstanding, we encourage ongoing study of additional patients with candidate phenotypes. Further, our results are consistent with the notion that other unknown copper-related transporters could be involved in diseases.

Blotting, Northern↗
PubMed2003

Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness.

Recessive mutations of SLC26A4 (PDS) are a common cause of Pendred syndrome and non-syndromic deafness in western populations. Although south and east Asia contain nearly one half of the global population, the origins and frequencies of SLC26A4 mutations in these regions are unknown. We PCR amplified and sequenced seven exons of SLC26A4 to detect selected mutations in 274 deaf probands from Korea, China, and Mongolia. A total of nine different mutations of SLC26A4 were detected among 15 (5.5%) of the 274 probands. Five mutations were novel and the other four had seldom, if ever, been identified outside east Asia. To identify mutations in south Asians, 212 Pakistani and 106 Indian families with three or more affected offspring of consanguineous matings were analysed for cosegregation of recessive deafness with short tandem repeat markers linked to SLC26A4. All 21 SLC26A4 exons were PCR amplified and sequenced in families segregating SLC26A4 linked deafness. Eleven mutant alleles of SLC26A4 were identified among 17 (5.4%) of the 318 families, and all 11 alleles were novel. SLC26A4 linked haplotypes on chromosomes with recurrent mutations were consistent with founder effects. Our observation of a diverse allelic series unique to each ethnic group indicates that mutational events at SLC26A4 are common and account for approximately 5% of recessive deafness in south Asians and other populations.

Asia, Southeastern↗
PubMed2001

Effect of metal ions on the stability of metallothionein in the degradation by cellular fractions in vitro.

Metallothioneins (MT), small molecular weight metal binding proteins are known to play an important protective role against heavy metal toxicity, either as antioxidants or pre-oxidants. However, the mode of metabolic fate of MTs in various metal complexes is not clearly understood. This study was carried out to better understand the mode of selective turnover rate of various form of MT in complexes with different metals. The degradation of in vitro translated mouse 35S-cysteine-MT was examined in lysosomal or cytosolic fractions from mouse liver by gel electrophoresis and autoradiography. Overnight incubations of MT showed extensive proteolysis in the lysosomal fraction but not in cytosolic fractions. However, Cu2+-MT was found to be stable under the same experimental condition. In contrast, Zn did not interfere with MT degradation. These results suggest that lysosomes are chiefly responsible for MT removal and appears to be selective on the metals involved in the MT complex. In vitro, translated, radiolabeled MT provides a suitable substrate for investigating the characteristics of MT degradation.

Animals↗
PubMed2001

Therapeutic trial in the first three Asian cases of ethylmalonic encephalopathy: response to riboflavin.

Three Korean girls with ethylmalonic encephalopathy, the first Asian cases, were identified. In all three cases, we observed slight improvement in motor functions, cognitive behaviours and chronic mucoid diarrhoea after treatment with riboflavin and/or coenzyme Q10 treatment. The precise pathogenesis of ethylmalonic encephalopathy has not been fully elucidated, but riboflavin treatment may be helpful.

Brain Diseases, Metabolic, Inborn↗
PubMed2001

Color stability of glass-ionomers and polyacid-modified resin-based composites in various environmental solutions.

PURPOSE: To evaluate the degree of color stability of glass-ionomers (GIs) and polyacid modified resin-based composites (PMRBCs) in various environmental solutions. MATERIALS AND METHODS: Seven polyacid-based esthetic restorative materials were used: three chemical-cured GIs, one resin-modified GI and three polyacid-modified RBCs. A light-cured resin-based composite (RBC) (Z 100) was used as a control. Disk type specimens were prepared and were aged in four different solutions (deionized water, 0.1 mole acetic acid solution, 75% ethanol, and 10% hydrogen peroxide solution) for 1, 7, 14, 21, 28, and 56 days. The specimens were kept at 37 degrees C throughout the study. Color coefficients (CIE L*a*b*) were measured by a reflection spectrophotometer with SCE mode, and the surface of specimens was examined by a stereo zoom microscope. RESULTS: In deionized water, all specimens showed an acceptable color stability. All of the GIs and PMRBCs showed significant color change in 0.1 mole acetic acid solution. The light-cured resin-modified GI showed a significant color change in 75% ethanol solutions. 10% hydrogen peroxide solution resulted in degradation and a high degree of color change for chemical-cured GIs. The light-cured resin-modified GI and PMRBCs showed high color change in 10% hydrogen peroxide solution. The light-cured RBC (Control), showed excellent color stability in all experimental solutions.

Acetic Acid↗
PubMed2000

The first successful prenatal diagnosis on a Korean family with citrullinemia.

DNA prenatal diagnosis was successfully performed on a family with citrullinemia. The father carried the G324S mutation and the mother carried the IVS6-2A > G mutation in the argininosuccinate synthase gene. They had a previous child with citrullinemia who died in the week after birth owing to complicated hyperammonemia. The lost child turned out to be a compound heterozygote. DNA was extracted from the cultured amniotic cells after amniocentesis done at 18-week gestation. For the detection of the G324S mutation, the PCR and restriction fragment length polymorphism method was used, and for the IVS6-2A > G mutation, allele-specific PCR was performed. The fetus was found to carry G324S but not IVS6-2A > G, suggesting a heterozygote carrier. Pregnancy was continued and a healthy boy was born. Plasma amino acid analysis performed on the third day after birth was normal and the serial ammonia level was in the normal range. A molecular study on his genomic DNA after birth also agreed with the previous fetal DNA analysis. He is now 2-months old with normal growth and development.

Adult↗
PubMed2000

Mutation analysis of Korean patients with citrullinemia.

Citrullinemia is an autosomal recessive disease due to the mutations in the argininosuccinate synthetase (ASS) gene. Mutation analysis was performed on three Korean patients with citrullinemia. All of the three patients had the splicing mutation previously reported as IVS6-2A>G mutation. Two had Gly324Ser mutation and the other patient had a 67-bp insertion mutation in exon 15. The IVS6-2A>G mutation was reported to be found frequently in Japanese patients with citrullinemia, but Caucasian patients showed the extreme mutational heterogeneity. Although a limited number of Korean patients were studied, the IVS6-2A>G mutation appears to be one of the most frequent mutant alleles in Korean patients with citrullinemia. The Gly324Ser mutation identified in two patients also suggests the possible high frequency of this mutation in Korean patients as well.

Alleles↗
PubMed2000

Hepatocellular carcinoma despite long-term survival in chronic tyrosinaemia I.

Tyrosinaemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma, in childhood or early adolescence. We studied a 37-year-old woman with tyrosinaemia I whose severe liver disease in infancy and rickets during childhood resolved with dietary therapy. From 14 years of age she resumed an unrestricted diet with the continued presence of the biochemical features of tyrosinaemia, yet maintained normal liver function. In adult years she accumulated only small amounts of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6-1g>t, and a novel missense mutation, Q279R. Studies of resected liver demonstrated the absence of hydrolytic activity and of immunological expression of fumarylacetoacetate hydrolase in liver tumour. In nontumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase was found. This case demonstrates the high risk of liver cancer in tyrosinaemia I even in a seemingly favourable biological environment.

Adult↗
PubMed2000

Connexin26 mutations associated with nonsyndromic hearing loss.

OBJECTIVE: Mutations in the GJB2 gene are a major cause of autosomal recessive and sporadic types of congenital deafness. The 35delG mutation is the most frequent type of mutation in white populations. However, several other forms were reported, such as 167delT among Ashkenazi Jews and R143W in Africans. The present study investigated the mutations of connexin26 (Cx26) found in patients with nonsyndromic hearing loss (NSHL) and newborns in the Korean population. STUDY DESIGN: The sequencing data for 147 unrelated patients with congenital NSHL and 100 audiologically screened newborns were included in this prospective study. METHODS: Genomic DNA samples from all patients and newborns were sequenced in both directions for detection of Cx26 mutations. RESULTS: Thirteen different types of mutations were found in the patients and newborns. V27I and E114G are the popular types of polymorphic mutations in both groups. 235delC-deletion and frameshift--was detected in patients (15 in 294 alleles) and newborns (1 in 200 alleles). 35delG was rarely found in both group. In addition to above mutations, several types of mutations--S85P, K41R, S72C, V84A, 176-191del, and 299-300del-were identified. The family study of the 235delC showed a typical autosomal recessive trait of NSHL in their audiological evaluation of hearing threshold. CONCLUSION: The frequency of 235delC allele showed much higher in the patients (5%) than in newborns (0.5%). We rarely found 35delC mutant in both groups. These results suggest that the different types of Cx26 mutations affect autosomal recessive NSHL according to ethnic background.

Adult↗
PubMed2000

MR arthrography of the labral capsular ligamentous complex in the shoulder: imaging variations and pitfalls.

OBJECTIVE: Using MR arthrography, we examined normal anatomy, anatomic variations, and pitfalls of imaging the labral capsular ligamentous complex in the asymptomatic shoulder. SUBJECTS AND METHODS: We obtained 108 MR arthrograms of the glenohumeral joint in 95 asymptomatic volunteers with axial (108 shoulders) and oblique coronal (56 shoulders) images. We examined labral shape, patterns of capsular insertion, presence or absence of glenohumeral ligaments, and pitfalls of imaging. Our patients were men (auxiliary policemen) between 19 and 24 years old (mean age, 21 years). RESULTS: The shapes of labra were triangular (anterior part, 64%; posterior part, 47%), round (17%; 33%), flat (2%; 17%), cleaved (11%; 1%), notched (3%; 0%), or absent (2%; 2%). Using the system of Mosely and Overgaard, the anterior capsular insertion was type 1 in 63% of shoulders, type 2 in 20%, and type 3 in 17%; the posterior capsular insertion was type 1 in 60% of shoulders, type 2 in 31%, and type 3 in 9%. The superior and inferior glenohumeral ligaments were present in 99% of shoulders, but the middle glenohumeral ligament was present in only 79%. We also detected many pitfalls of MR imaging in identifying findings such as the undercutting of the labrum by cartilage (32% of shoulders), prominent axillary folds (46%), sublabral holes (7%) or recesses (33%), Buford complexes (2%), and sulci between the biceps tendon and superior labrum (30%). CONCLUSION: Knowledge of normal anatomy and anatomic variations of the labral complex is important for the examination of the shoulder with MR arthrography.

Adult↗
PubMed2000

HFE gene mutation, C282Y causing hereditary hemochromatosis in Caucasian is extremely rare in Korean population.

Hereditary hemochromatosis (HFE), which affects 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals in Western population, results in multiple organ damage caused by iron deposition, and is treatable if detected early. C282Y mutation in HFE gene has been known to be responsible for the most hereditary hemochromatosis cases and 5-10% of white subjects are heterozygous for this mutation. However, the prevalence of hemochromatosis in the Asian population was reported to be very low and ethnic heterogeneity has been suspected. The aim of our study was to determine the prevalence of heterozygosity and homozygosity for the C282Y HFE gene mutations in 502 unrelated Koreans. Results revealed that none of them had the mutant gene, suggesting a significant ethnic difference when compared with Caucasians. Our study excluded underlying possibility of hereditary hemochromatosis in Korean which could mimic the findings of alcoholic liver disease with iron overload or liver cirrhosis with chronic hepatitis C.

Alleles↗
PubMed1999

Cloning and characterization of the promoter region of the Wilson disease gene.

Wilson disease (WD), an autosomal recessive disorder of copper transport, is marked by impaired biliary excretion and incorporation of copper into ceruloplasmin. Molecular mechanism regulating the expression of the WD gene was studied. We isolated, sequenced, and characterized approximately 1.3 kb of the 5'-flanking region of the WD gene from the human genomic library. The approximately 1.3 kb of the WD sequence directed high level of luciferase activity in HepG2 cells. Interestingly, the 5'-flanking region contained four metal response elements (MREs) and six MRE-like sequences (MLSs), usually found in the metallothionein genes. It also contained a number of putative regulatory elements such as Sp1, AP-1, AP-2, and E-box, but lacked TATA box. The transcription start site was located at 335 base pairs upstream of the translation initiation site. Successive 5'-deletion analyses suggested that the 159-base pair region from -811 to -653, which includes MLS2 (-802 to -796) and MLS3 (-785 to -779), contained one or more positive regulatory element(s). A negative element was also identified at region -1038 to -812. A protein-MLS complex was identified through electrophoretic mobility shift and competition assay using MLS2/MLS3 and HepG2 cell nuclear proteins.

Amino Acid Sequence↗