Biomedical subjects

X H Guo

Publications and source records attributed to X H Guo.

At least 19 recordsLinked to original sources

PubMed2000

Correlation of coronary angiography with "tombstoning" electrocardiographic pattern in patients after acute myocardial infarction.

BACKGROUND: It has been suggested that a specific pattern of electrocardiographic (ECG) changes following acute myocardial infarction (AMI), the so-called "tombstoning," predicts a poorer outcome, although the cause and associations of such changes are not known. To address the possible cause and implications, we correlated angiographic findings with tombstoning in patients following AMI. METHODS: The study investigated 124 patients with AMI, whose ECGs were taken within 24 h of onset of symptoms and who subsequently underwent angiography. In this population, 24 (19%) patients had a definite tombstoning pattern on their admission ECG. RESULTS: Compared with non-tombstoning ECGs, the significant differences in the tombstoning group are as follows: (1) All patients, including those with inferior infarction, had either total or partial occlusion of the left anterior descending (LAD) artery (100 vs. 44%, p < 0.0001); (2) LAD occlusions were significantly more severe and mostly proximal (100% occlusion: 50 vs. 20.5%, p = 0.02; <50% occlusion: 0 vs. 15.9% p = 0.039; proximal occlusion: 92 vs. 65%, p = 0.017); (3) patients with tombstoning ECGs had a significantly greater incidence of occlusion of all three coronary arteries (54.1 vs. 22%, p = 0.001); (4) tombstoning ECGs were more strongly associated with anterior than with inferior infarction (83.3 vs. 33%, p < 0.0001). CONCLUSIONS: The patients with a tombstoning pattern on the admission ECG, who underwent angiography, were associated with occlusion of a high-grade stenosis of the proximal LAD artery (usually with involvement of more than one artery) and were predominantly seen in association with anterior infarction.

Adult↗

PubMed2000

Consistency of multicenter measurements of heart rate variability in survivors of acute myocardial infarction.

Heart rate variability (HRV) analysis from 24-hour ambulatory ECG has been widely used in risk stratification of patients after myocardial infarction (MI). The accuracy of HRV assessment is known to potentially vary when different commercial systems are used. However, the consistency of HRV measurements has never been fully investigated. Twenty-six post-MI patients (mean age 59 +/- 8 years, 22 men) were studied, of whom 13 succumbed to sudden cardiac death (SCD) within 1 year and 13 remained alive for at least 3 years (MI survivors). Each patient had a 24-hour Holter ECG recorded before hospital discharge. HRV analysis was performed four times from the same recordings using three different Holter tape analysis systems (Marquette, Reynolds, and CardioData) by four independent operators (CardioData system was used twice, once in the United Kingdom and once in the United States). Mean normal-to-normal RR intervals (mNN) and 3 HRV parameters (SDNN, RMSSD, and HRV triangular index [HRVi]) were derived from each recording. The consistency of mNN and HRV measurements was evaluated by coefficient of variance (CV) and by the Bland-Altman method. The results demonstrated that (1) all indices measured by different systems were statistically similar (P = NS) except the measurement of RMSSD (P = 0.01), (2) the measurements of mNN were highly reproducible with a maximum mean difference of 1.8 +/- 13.8 ms and maximum limits of agreement from -14.6 to +15.6 ms. The maximum mean differences were--1.8 +/- 1.4 unit and 4.4 +/- 9.6 ms for HRVi and SDNN, respectively, and RMSSD was less reproducible with a maximum mean difference of--11.1 +/- 11.5 ms, and limits of agreement from -16.2 to +9.6 ms; and (3) the consistency of mNN (CV 0.9% +/- 0.9%) was significantly higher than that of HRVi, SDNN, and RMSSD (P < 0.0001). The consistency of HRVi was similar to that of SDNN (4.8% +/- 2.1% vs 5.7% +/- 4.8%, P = 0.4), and the consistency of RMSSD (26.6% +/- 13.3%) was significantly lower than that of the other measurements (P < 0.00001). In conclusion, the measurements of mNN by different analytical systems are the most consistent among the parameters studied. The global 24-hour measurements of HRV (SDNN and HRVi) are highly reproducible, whereas the measurement of short-term HRV components (RMSSD) is significantly less reproducible.

Adult↗

PubMed1999

Effect of moderate physical exercise on noninvasive cardiac autonomic tests in healthy volunteers.

BACKGROUND: In addition to the assessment of extreme cardiovascular reserve, new methodology is needed which is sensitive enough to detect subtle improvement in cardiovascular fitness in cardiac patients. AIM: This study modelled subtle clinical improvement by a moderate physical activity programme in healthy volunteers and investigated whether the improved fitness is detectable by non-invasive tests of cardiac autonomic status. METHODS: Twenty healthy volunteers (ten women, mean age 39.6+/-7.8 years) were divided into two groups of five women and five men in each. One group (the active group) was subjected to a moderate physical training programme for 6 months. The other group (the passive group) served as controls and continued with a predominantly sedentary lifestyle. Twice before commencing the exercise programme and regularly afterwards, subjects were investigated by a series of non-invasive autonomic tests including controlled respiration, active postural change, isometric handgrip, and Valsalva manoeuvre. A continuous three lead semi-orthogonal electrocardiogram and continuous blood pressure monitoring was obtained. Statistical descriptors of heart rate and blood pressure, spectral descriptors of their modulation, and baroreflex index giving the proportion between simultaneous heart rate and blood pressure changes were obtained from each test. RESULTS: Although the exercise programme was not extensive enough to be detected in changes of the baseline heart rate, the minimum RR interval during the Valsalva manoeuvre prolonged significantly with exercise in the active group. The mean arterial diastolic pressure decreased significantly. High frequency components of RR interval modulations decreased in supine controlled respiration and increased in standing controlled respiration and a trend towards an increase of both high frequency and low frequency components of diastolic arterial pressure modulations was noted with exercise. Baroreflex index assessed from Valsalva manoeuvre increased significantly. CONCLUSION: The study suggests that a selected set of non-invasive autonomic tests is sensitive enough to depict moderate improvement in cardiovascular fitness and that a multivariate assessment of cardiovascular fitness based on these tests might be applicable to monitoring chronic cardiac patients subjected to different clinical management modes.

Adult↗

PubMed1999

Dynamics of DNA molecules in gel studied by fluorescence microscopy.

The dynamics of individual DNA molecules in a thin gel were studied with fluorescence microscopy. Driven by an electric field, molecules hooked around isolated obstacles and became extended. By analyzing molecular images, we identified the reptation tube and primitive chain. When the field was turned off, the molecules relaxed. The relaxation time tau1 and primitive chain length at equilibrium depend on N, the size of the molecule in base pairs, consistently with reptation theory. Using five yeast chromosomal DNAs ranging in size from 245 kb to 980 kb, we found that: These results constitute a way of sizing individual DNA molecules by imaging rather than by gel electrophoresis.

Chromosomes, Fungal↗

PubMed1999

Relation of ventricular repolarization to cardiac cycle length in normal subjects, hypertrophic cardiomyopathy, and patients with myocardial infarction.

BACKGROUND: Prolonged QT interval and QT dispersion have been reported to reflect an increased inhomogeneity of ventricular repolarization, which is believed to be responsible for the development of arrhythmic events in patients with long QT syndrome, coronary heart disease, and myocardial infarction, congestive heart failure, and hypertrophic cardiomyopathy (HC). HYPOTHESIS: This study was undertaken to determine whether an abnormal QT/RR dynamicity may reflect autonomic imbalance and may contribute to arrhythmogenesis in patients with heart disease. METHODS: The relation between QT, QTpeak (QTp), Tpeak-Tend (TpTe) intervals and cardiac cycle length was assessed in 70 normal subjects, 37 patients with HC, and 48 survivors of myocardial infarction (MI). A set of 10 consecutive electrocardiograms was evaluated automatically in each subject using QT Guard software (Marquette Medical Systems, Milwaukee, Wisc.). RESULTS: In patients with HC, all intervals were significantly prolonged compared with normals (p < 0.001 for QT and QTp; p < 0.04 for TpTc); in survivors of MI, this was true for the maximum QT and QTp intervals (p < 0.05). A strong linear correlation between QT, QTp, and RR intervals was observed in normals and in patients with MI and HC (r = 0.65-0.59, 0.82-0.77, 0.79-0.74, respectively, p < 0.0001). TpTe interval only showed a weak correlation with heart rate in normals (r = 0.24, p < 0.05) and was rate-independent in both patient groups (p = NS). Compared with normals, the slopes of QT/RR and QTp/RR regression lines were significantly steeper in patients with MI and HC (0.0990-0.0883, 0.1597-0.1551, 0.1653-0.1486, respectively). Regression lines were neither parallel nor identical between normals and patients (T > 1.96, Z > 3.07). There was no difference in steepness for TpTeR/RR lines between groups (0.0110, 0.0076, 0.0163, respectively). TpTe/QTp ratio was similar in normals and in patients with MI and HC (0.30 +/- 0.03, 0.31 +/- 0.07, 0.30 +/- 0.04, respectively), in the absence of any correlation between QTp and TpTe intervals, suggesting disproportional prolongation of both components of QT interval. CONCLUSION: Compared with normals, a progressive increase in QT and QTp intervals at slower heart rates in patients with MI and HC may indicate an enhanced variability of the early ventricular repolarization and may be one of the mechanisms of arrhythmogenesis.

Adolescent↗

PubMed1999

Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes.

Sanfilippo B syndrome (mucopolysaccharidosis IIIB, MPS IIIB) is caused by a deficiency of alpha-N-acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes leads to degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. Age of onset and rate of progression vary considerably, whilst diagnosis is often delayed due to the absence of the pronounced skeletal changes observed in other mucopolysaccharidoses. Cloning of the gene and cDNA encoding alpha-N-acetylglucosaminidase enabled a study of the molecular basis of this syndrome. We were able to identify 31 mutations, 25 of them novel, and two polymorphisms in the 40 patients mostly of Australasian and Dutch origin included in this study. The observed allellic heterogeneity reflects the wide spectrum of clinical phenotypes reported for MPS IIIB patients. The majority of changes are missense mutations; also four nonsense and nine frameshift mutations caused by insertions or deletions were identified. Only five mutations were found in more than one patient and the observed frequencies are well below those observed for the common mutations in MPS IIIA. R643C and R297X each account for around 20% of MPS IIIB alleles in the Dutch patient group, whilst R297X, P521L, R565W and R626X each have a frequency of about 6% in Australasian patients. R643C seems to be a Dutch MPS IIIB allele and clearly confers the attenuated phenotype. One region of the gene shows a higher concentration of mutations, probably reflecting the instability of this area which contains a direct repeat. Several arginine residues seem to be 'hot-spots' for mutations, being affected by two or three individual base pair exchanges.

Acetylglucosaminidase↗

PubMed1998

QT dispersion and risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy.

This study examines the relation of QT dispersion (QTd) on a surface electrocardiogram (ECG) to clinical features and established risk factors of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HC). One hundred fifty-six consecutive patients with HC (91 men, mean age 41+/-15 years, range 7 to 79) and 72 normal subjects (41 men, mean age 39+/-9 years, range 20 to 60) were studied. Standard 12-lead ECGs were recorded from each subject using a MAC VU electrocardiograph. Patients with nonsinus rhythm, atrioventricular conduction block, QRS duration > 120 ms, age < 15 years, and low amplitude T waves were excluded from the analysis (n=51). Another 22 patients who were receiving amiodarone and/or sotalol therapy were also excluded. QT interval and QTd were measured using automated analysis in the remaining 83 patients (46 men, age 40+/-14 years, range 16 to 76). QT interval (406+/-38 ms), QTc interval (432+/-27 ms), and QTd (43+/-25 ms) were significantly greater in patients with HC than in normal controls (386+/-31 ms, 404+/-16 ms, 26+/-16 ms, respectively) (p <0.0001). QTd was significantly greater in patients with HC with chest pain compared with asymptomatic or mildly symptomatic patients (50+/-28 ms vs 37+/-20 ms, p=0.02). Increased QTd was found in patients with dyspnea New York Heart Association functional classes II/III than in those with dyspnea New York Heart Association functional class I (50+/-27 ms vs 38+/-22 ms, p=0.04). QTd was weakly correlated with maximum left ventricular wall thickness (r=0.228, p=0.038). No significant association was found between QTd and any risk factors for SCD. Thus, patients with HC have increased QTd. The QTd correlates with symptomatic status. Assessment of QTd might provide complementary clinical characterization of patients with HC but its relation to SCD remains uncertain.

Adolescent↗

PubMed1998

Circadian variation of the QT interval in patients with sudden cardiac death after myocardial infarction.

To evaluate the potential prognostic value of the circadian variation of QT intervals in predicting sudden cardiac death (SCD) in patients after myocardial infarction (MI), 15 pairs of post-MI patients (15 died suddenly within 1 year after MI [SCD victims] and 15 remained event-free [MI survivors]) were studied (mean age 60 +/- 8 years; 24 men and 6 women). The pairs were matched for age, gender, infarct site, presence of Q wave, left ventricular ejection fraction, thrombolytic and beta-blocker therapy. Fourteen normal subjects served as controls (mean age 55 +/- 9 years; 12 men). A 24-hour Holter electrocardiographic (ECG) recording was obtained from each subject. All recordings were analyzed using a Holter ECG analyser. QT, RR, and heart rate-corrected QT intervals (QTc) were automatically calculated by the analyzer, and hourly and 24-hour mean values of each measurement were derived from each recording. There was a pronounced circadian variation in the QT interval in parallel with the trend in the RR interval in normal subjects and in MI survivors. Circadian variation in both indexes was blunted in SCD victims. The QT interval was significantly longer at night than during the day in normal subjects (388 +/- 28 vs 355 +/- 21 ms, p = 0.001) and in MI survivors (358 +/- 25 vs 346 +/- 15 ms, p = 0.008), but not in SCD victims (357 +/- 32 vs 350 +/- 31 ms, p = 0.6). The 24-hour mean value of the QT interval in SCD victims did not differ significantly from that in normal subjects or MI survivors. The QT interval at night was significantly shorter in SCD victims than in normal subjects (357 +/- 32 vs 388 +/- 28 ms, p = 0.02), but daytime values were similar. The QT interval in SCD victims did not differ significantly from that of MI survivors at any time. The QTc interval exhibited a small circadian variation in normal subjects. This variation was abolished in SCD victims and MI survivors. The 24-hour mean value of QTc was significantly longer in SCD victims than in normal subjects (424 +/- 25 vs 402 +/- 21 ms, p = 0.02), and in MI survivors (424 +/- 25 vs 404 +/- 32 ms, p < 0.05). The QTc interval of SCD victims differed from that of normal subjects during both the day (421 +/- 25 vs 400 +/- 17 ms, p = 0.02) and night (424 +/- 26 vs 403 +/- 23 ms, p = 0.03). Thus, blunted circadian variation in QT intervals, abolished circadian variation in QTc intervals, and prolonged QTc intervals may suggest an increased risk of SCD in patients after MI.

Circadian Rhythm↗

PubMed1998

Exercise-induced changes in the QT interval duration and dispersion in patients with sudden cardiac death after myocardial infarction.

BACKGROUND: Prolongation of the QT interval and increased QT dispersion have been proposed to be associated with arrhythmic risk after myocardial infarction. However, controversy remains regarding the prognostic value of ventricular repolarization abnormalities in the risk stratification of patients surviving acute myocardial infarction. HYPOTHESIS AND OBJECTIVE: The QT interval is sensitive to myocardial ischaemia, and exercise-induced ischaemia may change the QT interval regionally, resulting in increased QT dispersion. This study examined whether there are abnormalities of ventricular repolarization during exercise and whether assessment of the exercise-induced changes in QT interval duration and dispersion would be able to differentiate patients at high risk from those at low risk of sudden cardiac death after myocardial infarction. METHODS: Twenty-six post-myocardial infarction patients (mean age 54.5+/-8.9 years, 22 men) were retrospectively studied. Thirteen patients who died suddenly (SCD patients) during a follow-up of 39+/-6 months were compared to 13 patients who remained event-free, i.e. no ventricular tachyarrhythmias, no reinfarction, no by-pass (MI survivors). The two groups were pair-matched for age, gender, site of infarction, left ventricular ejection fraction and use of beta blocker. A further 13 patients with chest pain, normal coronary arteriograms and negative exercise test results were studied as controls. They were age and gender matched with the post-infarction patients. A 12-lead exercise ECG was recorded from each patient before, during and after exercise. QT and RR interval were measured on the exercise ECGs at each stage and QT dispersion was defined as the difference between the maximum and minimum QT intervals across the 12-lead ECG. RESULTS: There were no significant differences in RR, QT and QTc (Bazett's and Fridericia's correction) intervals, or QT dispersion between any groups before exercise. A significant difference in QT and QT dispersion was found at peak exercise between post-infarction patients and controls (P=0.03 and P=0.0001, respectively), but no difference was observed between SCD patients and MI survivors. The maximum QTc at peak exercise was longer in SCD patients compared with MI survivors (P=0.02) and a maximum QTc>440 ms (Bazett's correction) was common in SCD patients but not in MI survivors or controls (62%, 15%, 15%, P=0.01). The differences in QT, QTc or QT dispersion observed at peak exercise were no longer significant after exercise. CONCLUSIONS: Exercise-induced prolongation of the QTc interval differentiates patients at high risk of sudden cardiac death from those at low risk, whereas exercise-induced changes in QT dispersion failed to identify patients at high risk of sudden cardiac death after myocardial infarction.

Adult↗

PubMed1998

Identification of a common mutation (R245H) in Sanfilippo A patients from The Netherlands.

We have identified a common mutation (R245H) in the sulphamidase gene of Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA, MPS IIIA) patients from The Netherlands. Allele-specific oligonucleotide hybridization was used to determine the incidence of this mutation in 45 unrelated MPS IIIA patients from different regions of The Netherlands. R245H was present in 51 alleles, representing 56.7% of the total allelic population. Of 39 patients, for whom we have uniform clinical details, 13 MPS IIIA patients who were homozygous for this common mutation had a more uniform but severe clinical phenotype than the remaining 21 or 5 patients, containing respectively one or no R245H alleles. The R245H allele had a higher prevalence in western rather than eastern regions of The Netherlands.

Adolescent↗

PubMed1998

Computerised measurements of QT dispersion in healthy subjects.

OBJECTIVE: To assess the stability and reproducibility of computerised QT dispersion (QTd) measurement in healthy subjects, as this is presently being incorporated into commercial electrocardiographic systems. METHODS: 70 healthy volunteers (mean (SD) age 38 (10) years, 35 men, 35 women) with a normal 12 lead electrocardiogram (ECG) were studied. From each subject, 70 ECG recordings were taken using the MAC VU ECG recorder (Marquette). In study A, 50 ECGs were recorded in each subject: 10 supine, 10 sitting, 10 standing, 10 holding breath in maximum inspiration, and 10 holding breath in maximum expiration. After a mean interval of 8 (3) days (range 7 to 23), 10 recordings in supine and 10 in the standing position were repeated in each subject (study B). On measurements made using a research version of the commercial software without manual modification, the reproducibility of QTd was assessed by coefficient of variance (CV) and relative error, and comparisons made with other ECG indices. RESULTS: (1) QTd measurements were stable and not influenced by changes in posture and respiratory cycle; (2) there was no difference in QTd measurements between men and women, or between age groups dichotomised at 35 years; (3) no correlation was found between QTd and heart rate or QT interval; (4) short term reproducibility of all QTd measurements (CV 15.6% to 43.8%) was worse than that of conventional ECG indices (CV 1.4% to 5.3%); (5) long term reproducibility of QTd measurements (relative error 27.4% to 31.0%) was also worse than that of conventional ECG indices (relative error 1.8% to 7.9%) (p < 0.0001); (6) the reproducibility of QTd measurements tended to increase when several serial recordings were averaged. CONCLUSIONS: Computerised measurements of global QTd and global QT-SD from 12 lead ECG by the MAC VU/QT Guard system are not significantly altered by changes in posture and respiration. The reproducibility of all QTd measurements is inferior to that of conventional ECG indices in healthy subjects.

Adolescent↗

PubMed1997

Mutations among Italian mucopolysaccharidosis type I patients.

A group of 27 Italian patients was screened for alpha-L-iduronidase mucopolysaccharidosis type I mutations. Mutations were found in 18 patients, with 28 alleles identified. The two most common mutations in northern Europeans (W402X and Q70X) accounted for 11% and 13% of the alleles, respectively. The R89Q mutation, uncommon in Europeans, was found only in one patient, accounting for 1 of 54 alleles (1.9%). The other mutations, P533R, A327P and G51D, accounted for 11%, 5.6% and 9.3% of the total alleles, respectively. Interestingly, the high frequency of the P533R mutation seems to be confined to Sicily and is higher than the 3% reported in a British/Australian study.

Adolescent↗

PubMed1997

Molecular defects in Sanfilippo syndrome type A.

Sanfilippo A syndrome (mucopolysaccharidosis type IIIA, MPS-IIIA) is an autosomal recessive neurodegenerative disorder due to an enzymatic defect of the lysosomal enzyme sulphamidase (EC 3.10.1.1) required for the degradation of heparan sulphate. In this study, molecular defects in the sulphamidase gene of MPS-IIIA patients were investigated in a group of 10 patients of Australian and American origin. The entire coding region of the sulphamidase gene was RT-PCR amplified and one polymorphism (R456H), four novel mutations (S66W, R245H, E447K, 1307 del 9) and one previously described mutation (1284 del 11) were identified by direct PCR sequencing. R245H was present in six patients including one severely affected homozygote. In three of the other patients with R245H, second mutant alleles were identified as S66W, 1284 del 11 and E447K, respectively. S66W was also detected in another patient where the other mutant allele remains undefined. In addition, 1307 del 9 was also detected in a patient with the other mutant allele remaining undefined. Allele specific oligonucleotide hybridisation was used to determine the incidence of these in a population of 26 MPS-IIIA patients (Australian and American) and 60 normal controls (Australian). R245H represented 27% (14/52 alleles) in this total patient population, while the other three changes ranged from 1.9 to 9.6% (1-5 of 52 alleles). The sequence variant, R456H, was shown to be polymorphic as it was present in 55% of normal and 38% of patient alleles. The total combined incidence of these five is 46% of alleles. This is the first study of the molecular defects in MPS-IIIA patients and will greatly assist the development of molecular analysis for MPS-IIIA patients and studies concerned with genotype to phenotype relationships.

Age of Onset↗

PubMed1997

Novel mutations in Sanfilippo A syndrome: implications for enzyme function.

Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) is an autosomal recessive lysosomal storage disorder caused by the deficiency of sulfamidase. The resulting lysosomal storage of heparan sulfate may lead to severe neurodegeneration preceded by progressive dementia, often combined with aggressive and hyperactive behaviour. A total of 109 patients from four different geographic areas were screened for the common mutation R245H and two other previously identified mutations. SSCP analysis of exons was used to characterize the unknown alleles. We identified 16 novel sequence variants, 12 of them likely to be pathogenic. The majority of the pathogenic variants were single base pair changes leading to missense mutations. Several single base pair deletions/insertions and one nonsense mutation were also identified. Altogether, we were able to characterize 55% of the pathogenic alleles. Sequence homology between sulfamidase and N-acetylgalactosamine 4-sulfatase, the first sulfatase to have its tertiary structure defined, suggests that amino acid residues R74 and T79, which were found to be mutated, are likely to be involved in the formation of the active site of sulfamidase. R245H accounts for 31% of the Sanfilippo A alleles in Australasia, for 19.2% of the alleles in patients from the UK and has a high frequency of 57.8% in patients from The Netherlands. The identification of mutations common in certain geographic regions or ethnic groups will help in the diagnosis of MPS IIIA and allow carrier testing and improved genetic counselling.

DNA Primers↗

PubMed1996

Structure and sequence of the human sulphamidase gene.

Sanfilippo A syndrome (MPS-IIIA) is a mucopolysaccharide lysosomal storage disorder caused by a deficiency in the lysosomal enzyme, sulphamidase (EC 3.10.1.1), which is required for the degradation of heparan sulphate. A genomic clone containing the entire sulphamidase gene was isolated from a chromosome 17-specific gridded cosmid library. The structure of the gene and the sequence of the exon/intron boundaries and the 5' promoter region were determined. The sulphamidase gene is split into 8 exons spanning approximately 11 kb.

Base Sequence↗

PubMed1995

Expression, purification and characterization of recombinant human N-acetylgalactosamine-6-sulphatase.

Full-length cDNA sequences encoding human N-acetylgalactosamine-6-sulphatase were stably expressed in Chinese hamster ovary cells under the transcriptional control of the human polypeptide chain elongation factor 1 alpha gene promoter. A clonal cell line overexpressing recombinant N-acetylgalactosamine-6-sulphatase to a level of approx. 3 mg/l of culture medium was isolated. The secreted precursor enzyme was purified to homogeneity by a two-column procedure with an overall yield of 53% of the activity. The physical and catalytic parameters of the recombinant enzyme were similar to those of the mature form isolated from liver. On SDS/PAGE and gel filtration, recombinant N-acetylgalactosamine-6-sulphatase had a native molecular mass of 58-60 kDa. Recombinant N-acetylgalactosamine-6-sulphatase was endocytosed by mucopolysaccharidosis IVA fibroblasts via the mannose-6-phosphate receptor-mediated pathway and was efficiently localized to lysosomes.

Animals↗

PubMed1995

Cloning of the sulphamidase gene and identification of mutations in Sanfilippo A syndrome.

Sanfilippo A syndrome is one of four recognised Sanfilippo sub-types (A, B, C and D) that result from deficiencies of different enzymes involved in the lysosomal degradation of heparan sulphate; patients suffer from severe neurological disorders. The Sanfilippo syndrome sub-types are also known as mucopolysaccharidosis (MPS) type III (MPS-IIIA, B, C and D), and are part of the large group of lysosomal storage disorders. Each of the MPS-III types is inherited as an autosomal recessive disorder with considerable variation in severity of clinical phenotype. The incidence of Sanfilippo syndrome has been estimated at 1:24,000 in The Netherlands with MPS IIIA (MIM #252900) the most common. MPS-IIIA is the predominant MPS-III in the United Kingdom, and has a similar high incidence to that found in The Netherlands (E. Wraith, personal communication). There is a particularly high incidence of a clinically severe form of MPS-IIIA in the Cayman Islands with a carrier frequency of 0.1 (ref. 4). Due to the mild somatic disease compared to other MPS disorders there is difficulty in diagnosing mild cases of MPS-III, hence Sanfilippo syndrome may be underdiagnosed, especially in patients with mild mental retardation. Here, we report the isolation, sequence and expression of cDNA clones encoding the enzyme sulphamidase (EC 3.10.1.1). In addition, we report the chromosomal localisation of the sulphamidase gene as being 17q25.3. An 11-bp deletion, present in sulphamidase cDNA from two unrelated Sanfilippo A patients, is described.

Amino Acid Sequence↗

PubMed1995

Human renin 5'-flanking DNA to nucleotide-2750.

Renin is one of the most important factors in blood pressure and electrolyte regulation in mammals and the renin locus has been implicated in hypertension. To assist studies of promoter control we therefore determined the 5'-flanking sequence of the human gene (REN) to residue -2750 relative to the transcription start site (+1). Sites of homology to consensus sequences for binding of trans-acting factors involved in transcriptional control of other genes were identified, and functionality for two of these (a CRE and Pit-1 site) have so far been demonstrated.

Base Sequence↗