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Biomedical subjects

M Boon

Publications and source records attributed to M Boon.

12 recordsLinked to original sources
PubMed2005

POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome.

BACKGROUND: Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterised by congenital muscular dystrophy, structural brain defects, and eye malformations. Typical brain abnormalities are hydrocephalus, lissencephaly, agenesis of the corpus callosum, fusion of the hemispheres, cerebellar hypoplasia, and neuronal overmigration, which causes a cobblestone cortex. Ocular abnormalities include cataract, microphthalmia, buphthalmos, and Peters anomaly. WWS patients show defective O-glycosylation of alpha-dystroglycan (alpha-DG), which plays a key role in bridging the cytoskeleton of muscle and CNS cells with extracellular matrix proteins, important for muscle integrity and neuronal migration. In 20% of the WWS patients, hypoglycosylation results from mutations in either the protein O-mannosyltransferase 1 (POMT1), fukutin, or fukutin related protein (FKRP) genes. The other genes for this highly heterogeneous disorder remain to be identified. OBJECTIVE: To look for mutations in POMT2 as a cause of WWS, as both POMT1 and POMT2 are required to achieve protein O-mannosyltransferase activity. METHODS: A candidate gene approach combined with homozygosity mapping. RESULTS: Homozygosity was found for the POMT2 locus at 14q24.3 in four of 11 consanguineous WWS families. Homozygous POMT2 mutations were present in two of these families as well as in one patient from another cohort of six WWS families. Immunohistochemistry in muscle showed severely reduced levels of glycosylated alpha-DG, which is consistent with the postulated role for POMT2 in the O-mannosylation pathway. CONCLUSIONS: A fourth causative gene for WWS was uncovered. These genes account for approximately one third of the WWS cases. Several more genes are anticipated, which are likely to play a role in glycosylation of alpha-DG.

Brain↗
PubMed2001

Mapping of a susceptibility gene for multiple sclerosis to the 51 kb interval between G511525 and D6S1666 using a new method of haplotype sharing analysis.

Multiple sclerosis (MS) is a complex disease that is partly genetic in origin. Although an association of MS with specific human leukocyte antigen (HLA) types has been known for almost 30 years, the nature of this relationship has remained unclear. Furthermore, genetic resolution sufficient to implicate a specific gene in the HLA region has not been achieved. Many loci in the HLA region have been found to be significantly associated with MS, which is largely explained by the extended haplotype sharing and varying marker informativity of the region. We have determined 248 haplotypes of MS patients from the population of the northern Netherlands and 226 haplotypes of their relatives as controls using a set of 22 microsatellite markers covering the HLA region. The data were analyzed using standard association methods and a new statistical method, haplotype sharing statistics (HSS). Haplotype sharing statistics determines the extent of haplotype sharing for all pairs of haplotypes of patients and of controls and calculates the difference in mean haplotype sharing between patients and controls. Haplotype sharing was found to be significantly greater among patients than among controls in a region of 1.1 Mb between markers G511525 and TNFalpha. The involvement of this region is also supported by association analysis and the transmission/disequilibrium test (TDT). Within this region, HSS, which is largely independent of association and TDT, indicated the interval of 51 kb between G511525 and D6S1666 as that most likely to contain a susceptibility gene for MS. As DQB1 is the sole gene known in this interval at present, the results of our analysis suggest that this gene plays a role in the pathogenesis of MS.

Cluster Analysis↗
PubMed1999

Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone: a pilot study.

The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral dexamethasone 16 mg per day (four divided doses) for 5 consecutive days. After one week, the expanded disability status scale (EDSS) had improved by one or more grades in 88% (22 patients) and after 4 weeks in 92% (23 patients). Treatment was well tolerated. We conclude that a course of oral dexamethasone 16 mg per day shortens the duration of an exacerbation in MS in a similar way as seen after high dose i.v. methylprednisolone. Although a randomized study is needed to test this treatment regimen against i.v. high dose corticosteroids, oral dexamethasone can be used in situations when i.v. therapy is difficult to apply. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1998

Effects of influenza vaccination and influenza illness on exacerbations in multiple sclerosis.

Despite reports that influenza vaccination appears to be safe in multiple sclerosis there is uncertainty which patients may benefit from it. By using a questionnaire we compared the effects of influenza illness (1995-1996 season) and influenza vaccination (autumn of 1996) on neurologic symptoms in patients with multiple sclerosis registered in the Groningen Multiple Sclerosis Data Bank. No clinically relevant effects were reported in 53 patients with primary progressive multiple sclerosis, either following vaccination or the illness. In a group of 180 patients with relapsing multiple sclerosis, an exacerbation occurred within the following 6 weeks in 33% after influenza illness, whereas it occurred in only 5% after vaccination. The exacerbation rate following influenza illness was significantly higher regardless of whether patients were essentially restricted to wheelchair or not. Because of a substantial greater risk of relapse after influenza illness than after vaccination, annual influenza vaccination should be offered routinely to all patients with relapsing multiple sclerosis.

Adult↗
PubMed1990

CRM+ haemophilia A due to a missense mutation (372----Cys) at the internal heavy chain thrombin cleavage site.

We have used the polymerase chain reaction (PCR) and differential oligonucleotide melting to screen for mutations in selected CpG dinucleotides in the factor VIII genes of haemophilia A patients. By this means we have identified and confirmed by sequencing a novel point mutation in codon 372 (CGC) of the factor VIII gene of a moderately severe CRM+ haemophiliac. The first C of this codon has been substituted by T resulting in the non-conservative substitution of cysteine for arginine at an essential thrombin cleavage site in factor VIII. Analysis of three intragenic restriction fragment length polymorphisms was uninformative in the patient's family. However, DNA analysis for the specific mutation shows one sister and the patient's mother to be carriers, and the other sister to be normal. This DNA analysis confirmed the results of phenotype analysis by factor VIII coagulant to von Willebrand factor antigen ratios for the females at risk. The two carrier females had low factor VIII coagulant activity and excess VIII antigen as predicted but the non-carrier sister also had anomalously high VIII antigen in her plasma. When feasible, mutation specific DNA analysis is able to resolve the difficulties posed by variable phenotype data and unknown level of mutation in sporadic haemophilia A.

Base Sequence↗
PubMed1990

[Minor seizures in young children: epileptic or not?].

In 80 children the clinical features of sudden changes of consciousness, motor activity and/or behavior were studied retrospectively. Epileptic and non-epileptic seizures could not be separated because of specific clinical characteristics in this population, although breath holding spells have some rather distinguishing features. The greatest problem was the lack of detailed clinical information in many cases. A group of children remains with paroxysmal events of unknown origin, but from this material the prognosis of them seems to be good. The clinician should be able to differentiate epileptic from non-epileptic seizures by taking a careful history based upon a detailed knowledge of the different kinds of both epileptic and non-epileptic attacks.

Child, Preschool↗
PubMed1984

Koilocytotic lesions of the cervix. The relationship of mitotic abnormalities to the presence of papillomavirus antigens and nuclear DNA content.

It has been reported that abnormal mitotic figures (AMFs) occur principally in aneuploid lesions and that aneuploidy is a diagnostic feature of non-endocrine-dependent epithelial cancer precursors and cancers. Recently, AMFs have been reported in cervical lesions interpreted as flat condylomata, and it has been suggested by several authors that AMFs may not be diagnostic or aneuploidy or neoplasia, particularly in human papillomavirus-(HPV)-induced lesions. Although it is conceivable that AMFs may be a regular feature of HPV infection, their association with cytologic atypia and their presence in higher grades of cervical intraepithelial neoplasia (CIN) suggests that AMFs may herald the presence of a different lesion than the pure flat condyloma. In the current study, koilocytotic cervical lesions thought to be HPV-induced were examined microscopically for the presence of AMFs, and the findings were correlated with the presence of HPV as determined by immunoperoxidase and nuclear DNA distribution patterns as measured by Feulgen microspectrophotometry. In unselected lesions originally diagnosed as flat cervical condylomata, AMFs were surprisingly common (22.6%), and did not correlate with the extent of koilocytosis. Immunoperoxidase (IMPO) stains were performed in 35 cases with AMFs, and were negative for HPV in 74.3% and positive in 22.8%. However, among the cases evaluated by IMPO, there was an inverse relationship between the presence of mitotic abnormalities and the expression of HPV antigen. Nine of 11 (81.8%) lesions containing AMFs were aneuploid, and 2 of 11 (18.2%) were polyploid. Abnormal mitotic figures have a range of morphology and frequency in koilocytotic cervical lesions. Although the biology of these lesions is not well-defined, the presence of AMFs may identify a subgroup of HPV-induced cervical atypias which represent a transition between flat cervical conylomata and CIN.

Animals↗
PubMedDate not supplied

Kinetics of ferrous iron oxidation by Leptospirillum bacteria in continuous cultures.

The oxidation of ferrous iron by Leptospirillum bacteria was studied in a continuous culture in the dilution rate range 0.009-0.077 h-1 and could be described with a rate equation for competitive ferric iron inhibition kinetics in terms of the ferric/ferrous iron ratio in the solution. The ferrous iron oxidation in the continuous culture was followed by means of oxygen and carbon dioxide concentration analyses in reference air and off-gas. From these measurements the oxygen consumption rate, rO2, the carbon dioxide consumption rate, rCO2, the biomass concentration, Cx, and the biomass specific oxygen consumption rate, qO2, in the culture were determined. The ferrous iron concentration in the culture was below accurate levels to determine with the usual titrimetric method and was therefore derived from measuring the solution redox potential. The degree of reduction balance was used to check the theoretically expected relation between the rates of ferrous iron, -rFe2+, oxygen, -rO2, and biomass, rx. The maximum biomass yield and maintenance coefficient on oxygen are Yoxmax = 0.047 mol of C/mol of O2 and mo = 0.057 mol of O2/(mol of C.h). The maximum specific oxygen consumption rate, qO2,max = 1.7 mol of O2/(mol of C.h), the affinity coefficient, Ks/Ki = 0.0005 mol of Fe2+/mol of Fe3+, and the maximum specific growth rate, micromax = 0.069 h-1, Ks/Ki = 0.0004, were fitted from the measured data. For several dilution rates, off-line respiratory measurements with cell suspension from the continuous culture were carried out in dynamic BOM-Eh measurements. The dissolved oxygen and redox potential were measured simultaneously and monitored. The measured value of qO2,max varied between 2.3 and 1.7 mol/(mol of C.h). The value of Ks/Ki = 0.0007 was equal in all experiments. The measured values of qO2 in the continuous culture were well described with the kinetics determined in dynamic BOM-Eh measurements. It was concluded that dynamic BOM-Eh measurements are a convenient method to determine the kinetics of continuous culture grown Leptospirillum bacteria.

Bacteria↗