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Biomedical subjects

M Goossens

Publications and source records attributed to M Goossens.

At least 19 recordsLinked to original sources
PubMed2006

Very low prevalence of germline MSH6 mutations in hereditary non-polyposis colorectal cancer suspected patients with colorectal cancer without microsatellite instability.

Hereditary non-polyposis colorectal cancer (HNPCC) is caused by mutations in one of the mismatch repair genes MLH1, MSH2, MSH6, or PMS2 and results in high-level microsatellite instability (MSI-high) in tumours of HNPCC patients. The MSI test is considered reliable for indicating mutations in MLH1 and MSH2, but is questioned for MSH6. Germline mutation analysis was performed in 19 patients with an MSI-high tumour and absence of MSH2 and/or MSH6 protein as determined by immunohistochemistry (IHC), without an MLH1 or MSH2 mutation, and in 76 out of 295 patients suspected of HNPCC, with a non-MSI-high colorectal cancer (CRC). All 295 non-MSI-high CRCs were analysed for presence of MSH6 protein by IHC. In 10 patients with an MSI-high tumour without MSH2 and/or MSH6 expression, a pathogenic MSH6 mutation was detected, whereas no pathogenic MSH6 mutation was detected in 76 patients with a non-MSI-high CRC and normal MSH6 protein expression. In none of the 295 CRCs loss of MSH6 protein expression was detected. The prevalence of a germline MSH6 mutation is very low in HNPCC suspected patients with non-MSI-high CRC. Microsatellite instability analysis in CRCs is highly sensitive to select patients for MSH6 germline mutation analysis.

Adult↗
PubMed2006

Damping of magnetohydrodynamic waves by resonant absorption in the solar atmosphere.

In the last decade we have been overwhelmed by an avalanche of discoveries of magnetohydrodynamic (MHD) waves by the Solar and Heliospheric Observatory and Transition Region and Coronal Explorer observatories. Both standing and propagating versions of fast magnetoacoustic and slow magnetoacoustic MHD waves have been detected. Information on the damping times and damping distances of these waves is less detailed and less accurate than that on periods and amplitudes. Nevertheless, observations show the damping times and damping lengths are often short. Also, different types of MHD waves in different types of magnetic structures likely require different damping mechanisms. The phenomenon of fast damping is well documented for the standing fast magnetosonic kink waves in coronal loops. This paper concentrates on standing fast magnetosonic waves. It reports on results on periods and damping times due to resonant absorption in one-dimensional and two-dimensional models of coronal loops. Special attention is given to multiple modes.

Journal Article↗
PubMed2006

Quasi-mode damping in two-dimensional fully non-uniform coronal loops.

Resonantly damped fast kink quasi-modes are computed in fully resistive magnetohydrodynamics for fully non-uniform two-dimensional equilibrium models. The equilibrium model is a straight cylindrically symmetric flux tube with a plasma density that is non-uniform both across and along the loop. The variation of density across the loop can cover the whole loop. Our results indicate that the period and damping of coronal loop oscillations mainly depend on the density contrast and the inhomogeneity length-scale and are independent of the details of longitudinal stratification. This study extends previous studies on coronal loop oscillations, and allows for a better comparison between observations and theory.

Journal Article↗
PubMed2006

A new large CFTR rearrangement illustrates the importance of searching for complex alleles.

The p.Val754Met variant, described in 1996 in a CF patient, has been considered a CF mutation. However, biochemical aspects, results of functional studies and, finally, the identification of a complex deletion removing exons 3 to 10 and 14b to 16 in cis of p.Val754Met in a CF patient, argue against a strong deleterious effect. An inventory through the French CF network of patients carrying p.Val754Met led to the registration of seven patients (CF: n=4; idiopathic chronic pancreatitis: n=3) and six healthy individuals, all heterozygous for the variation. Extensive CFTR gene analysis was carried out, including the search for large rearrangements and other possible mutations. The complex deletion, whose breakpoints are described here, was found only in the four CF patients, in association with the same haplotype. This data, added to the fact that the p.[Phe508del]+[Val754Met] genotype was found in a healthy individual, bring further arguments against the association of p.Val754Met with CF. We thus suggest looking for a possible complex allele whenever p.Val754Met is detected and considering it neutral regarding genetic counseling when found in isolation.

Adolescent↗
PubMed2006

Influence of mattress characteristics on house dust mite allergen concentration.

BACKGROUND: Exposure to a high level of house dust mite allergens (HDMAs) is considered as a risk factor for HDM sensitization and development of asthma in genetically disposed people. Mattresses are one of the most important sources of HDMA in people's living environment. OBJECTIVE: The aim of this study was to evaluate the association between mattress characteristics and HDMA concentrations on mattresses. METHODS: Dust samples of mattress surfaces were taken to evaluate the level of Der p 1 allergen. All participants filled in a questionnaire about the type of mattress, the type of covering (upper layer) of the mattress, dwelling characteristics and cleaning habits. Humidity and temperature of the bedroom were measured at the time of dust sampling. RESULTS: One hundred and sixty-eight questionnaires were filled in. Synthetic upper layer of the mattress was associated with a higher level of Der p 1 compared with cotton upper layer (2.6 vs. 0.8 microg/g Der p 1). Moreover, higher relative humidity (RH) was associated with significant higher concentrations and density of Der p 1. CONCLUSIONS: Two factors were associated with lower levels of Der p 1 found on mattresses, namely: a cotton upper layer of the mattress compared with a layer of synthetic material and lower RH at the time of sampling. As far as we know, the association between type of upper layer and concentration of Der p 1 has not been described before and could lead to the formulation of practical advices in order to reduce HDMA concentrations on mattresses.

Air Pollution, Indoor↗
PubMed2005

Cross-scale nonlinear coupling and plasma energization by Alfvén waves.

We present a new channel for the nonlocal transport of wave energy from the large (MHD) scales to the small (kinetic) scales generated by the resonant decay of MHD Alfvén waves into kinetic Alfvén waves. This process does not impose any restriction on the wave numbers or frequencies of initial MHD waves, which makes it superior compared to the mechanisms of spectral transport studied before. Because of dissipative properties of the nonlinearly driven kinetic Alfvén waves, the decay leads to plasma heating and particle acceleration, which is observed in a variety of space and astrophysical plasmas. Two examples in the solar corona and the terrestrial magnetosphere are briefly discussed.

Journal Article↗
PubMed2005

Comprehensive cystic fibrosis mutation epidemiology and haplotype characterization in a southern Italian population.

We screened the whole coding region of the cystic fibrosis transmembrane regulator (CFTR) gene in 371 unrelated cystic fibrosis (CF) patients from three regions of southern Italy. Forty-three mutations detected 91.5% of CF mutated chromosomes by denaturing gradient gel electrophoresis analysis, and three intragenic CFTR polymorphisms predicted a myriad of rare mutations in uncharacterized CF chromosomes. Twelve mutations are peculiar to CF chromosomes from southern Italy: R1158X, 4016insT, L1065P and 711 + 1G > T are present in 6.3% of CF chromosomes in Campania; G1244E and 852del22 are present in 9.6% of CF chromosomes in Basilicata and 4382delA, 1259insA, I502T, 852del22, 4016insT, D579G, R1158X, L1077P and G1349D are frequent in Puglia (19.6% of CF alleles). Several mutations frequently found in northern Italy (e.g., R1162X, 711 + 5G > T) and northern Europe (e.g., G551D, I507del and 621 + 1G > T) are absent from the studied population. The I148T-3195del6 complex allele was present in two CF chromosomes, whereas I148T was present in both alleles (as a single mutation) in another CF patient and in five CF carriers; this could result from crossover events. The haplotype analysis of three intragenic polymorphisms (IVS8CA, IVS17bTA and IVS17bCA) compared with data from other studies revealed that several mutations (3849 + 10kbC > T, 1717-1G > A, E585X, 3272-26G > A, L558S, 2184insA and R347P) originated from multiple events, whereas others (R1158X and S549R) could be associated with one or more intragenic recombinant events. Given the large population migration from southern Italy, knowledge of the CF molecular epidemiology in this area is an important contribution to diagnosis, counselling and interlaboratory quality control for molecular laboratories worldwide.

Cystic Fibrosis↗
PubMed2004

Large differences in cost of illness and wellbeing between patients with fibromyalgia, chronic low back pain, or ankylosing spondylitis.

OBJECTIVE: To compare the cost of illness of three musculoskeletal conditions in relation to general wellbeing. METHODS: Patients with fibromyalgia, chronic low back pain (CLBP), and ankylosing spondylitis who were referred to a specialist and participated in three randomised trials completed a cost diary for the duration of the study, comprising direct medical and non-medical resource utilisation and inability to perform paid and unpaid work. Patients rated perceived wellbeing (0-100) at baseline. Univariate differences in costs between the groups were estimated by bootstrapping. Regression analyses assessed which variables, in addition to the condition, contributed to costs and wellbeing. RESULTS: 70 patients with fibromyalgia, 110 with chronic low back pain, and 111 with ankylosing spondylitis provided data for the cost analyses. Average annual disease related total societal costs per patient were 7813 euro for fibromyalgia, 8533 euro for CLBP, and 3205 euro for ankylosing spondylitis. Total costs were higher for fibromyalgia and CLBP than for ankylosing spondylitis, mainly because of cost of formal and informal care, aids and adaptations, and work days lost. Wellbeing was lower in fibromyalgia (mean, 48) and low back pain (mean, 42) than in ankylosing spondylitis (mean, 67). No variables other than diagnostic group contributed to differences in costs or wellbeing. CONCLUSIONS: In patients under the care of a specialist, there were marked differences in costs and wellbeing between those with fibromyalgia or CLBP and those with ankylosing spondylitis. In particular, direct non-medical costs and productivity costs were higher in fibromyalgia and CLBP.

Adult↗
PubMed2004

Atypical sinusitis in adults must lead to looking for cystic fibrosis and primary ciliary dyskinesia.

UNLABELLED: HYPOTHESES/OBJECTIVES:: In adults, purulent pansinusitis or nasal polyposis starting early in life or that is permanently infected or associated either with chronic bronchial infection, infertility, or situs inversus are uncommon. In these atypical cases of chronic sinusitis (ACS), a primary dysfunction of the mucociliary clearance can be suspected. Adult patients with ACS were therefore investigated to detect primary ciliary dyskinesia (PCD) or cystic fibrosis (CF). STUDY DESIGN: Open, prospective study. PATIENTS AND METHODS: Forty-two patients with ACS were investigated with ciliary beat frequency and ultrastructure analysis in nasal cells and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis in blood leukocytes. RESULTS: The diagnosis of PCD was confirmed in seven (17%) patients. At least one CFTR gene mutation was detected in 16 (38%) patients. The diagnosis of CF was suggested in three (7%) compound heterozygous patients. Another 13 (31%) patients were heterozygous for a CFTR gene mutation or a complex allele. Comparison of clinical features of ACS showed that only a family history of chronic sinusitis (P <.01) or chronic bronchitis (P <.02) and the presence of diffuse bronchiectasis (P <.0001) or serous otitis media (P <.0001) were significantly more frequent in PCD patients than in patients carrying CFTR gene mutations or those without PCD or CFTR gene mutations. CONCLUSIONS: ACS should be considered a remarkable entity in which congenital abnormalities of epithelial cells are frequently detected (55% of patients). The higher frequency of mutations in ACS patients compared with the general population suggests that heterozygoty for CFTR gene mutation could be a sinusitis-causing status.

Adult↗
PubMed2003

Mowat-Wilson syndrome.

MWS is a multiple congenital anomaly syndrome, first clinically delineated by Mowat et al in 1998. Over 45 cases have now been reported. All patients have typical dysmorphic features in association with severe intellectual disability, and nearly all have microcephaly and seizures. Congenital anomalies, including Hirschsprung disease (HSCR), congenital heart disease, hypospadias, genitourinary anomalies, agenesis of the corpus callosum, and short stature are common. The syndrome is the result of heterozygous deletions or truncating mutations of the ZFHX1B (SIP1) gene on chromosome 2q22.

Abnormalities, Multiple↗
PubMed2001

Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot-Marie-Tooth disease, is directly regulated by the transcription factor SOX10.

Mutations in SOX10, a transcription modulator crucial in the development of the enteric nervous system (ENS), melanocytes and glial cells, are found in Shah-Waardenburg syndrome (WS4), a neurocristopathy that associates intestinal aganglionosis, pigmentation defects and sensorineural deafness. Expression of MITF and RET, two genes that play important roles during melanocyte and ENS development, respectively, are controlled by SOX10. The observation that some WS4 patients present with myelination defects of the central and peripheral nervous systems correlates with the recent finding that P(0), a major component of the peripheral myelin, is another transcriptional target of SOX10. These phenotypic features suggest that SOX10 could regulate expression of other genes involved in the myelination process as well. Thus, we tested the ability of SOX10 to regulate expression of MBP, PMP22 and Connexin 32, three major proteins of the peripheral myelin. Our study shows that this factor, in synergy with EGR2, strongly activates Cx32 expression in vitro by directly binding to its promoter. In agreement with this finding, SOX10 and EGR2 mutants identified in patients with peripheral myelin defects fail to transactivate the Cx32 promoter. Moreover, we show that a mutation of the Cx32 promoter previously described in a patient with the X-linked form of Charcot-Marie-Tooth (CMTX) disease impairs SOX10 function. In addition to providing new insights into the molecular mechanisms underlying some of the peripheral myelin defects observed in CMTX disease, these results further extend the spectrum of genes that are regulated by SOX10.

Binding Sites↗
PubMed2001

Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a syndromic Hirschsprung disease.

Hirschsprung disease (HD) has been described in association with microcephaly, mental retardation and characteristic facial features, delineating a syndrome possibly caused by mutations localized at chromosome 2q22--q23. We have analyzed a de novo translocation breakpoint at 2q22 in one patient presenting with this syndrome, and identified a gene, SIP1, which is disrupted by this chromosomal rearrangement. SIP1 encodes Smad interacting protein 1, a new member of the delta EF1/Zfh-1 family of two-handed zinc finger/homeodomain transcription factors. We determined the genomic structure and expression of the human SIP1 gene. Further analysis of four independent patients showed that SIP1 is altered by heterozygous frameshift mutations causing early truncation of the protein. SIP1, among other functions, seems to play crucial roles in normal embryonic development of neural structures and neural crest. Its deficiency, in altering function of the TGF beta/BMP/Smad-mediated signalling cascade, is consistent with some of the dysmorphic features observed in this syndrome, in particular the enteric nervous system defect that underlies HD.

Abnormalities, Multiple↗
PubMed2001

The SOX10 transcription factor: evaluation as a candidate gene for central and peripheral hereditary myelin disorders.

The SOX10 transcription factor is involved in development of neural crest derivatives and fate determination in glial cells. SOX10 mutations have been found in patients with intestinal aganglionosis and depigmentation with deafness (Waardenburg-Hirschsprung). Associated neurological signs have been reported in some cases, including a patient exhibiting a central and peripheral myelin deficiency. Therefore, we screened for SOX10 mutations in a large cohort of patients with peripheral and central myelin disorders. 56 were affected by classical demyelinating Charcot-Marie-Tooth disease without identified mutations in the genes encoding PNS myelin proteins (PMP22, P0), connexin 32 and the zinc-finger transcription factor, EGR2. 88 patients with undetermined leukodystrophy were selected from a large European prospective study. Associated clinical, magnetic resonance imaging and electrophysiological signs were consistent with a defect in CNS myelination in 83 and with an active degeneration of the CNS myelin in 5. No abnormalities in the proteolipid protein gene (PLP) were found. The absence of SOX100 mutation in this large cohort of patients suggests that this gene is not frequently involved in peripheral or central inherited myelin disorders.

Charcot-Marie-Tooth Disease↗
PubMed2001

Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations.

Seventy-nine unrelated Lebanese patients were tested for 15 mutations in the MEFV gene: A761H, A744S, V726A, K695R, M694V, M694I, M694del, M6801 (G --> C), M680I (G --> A) in exon 10, F479L in exon 5, P369S in exon 3, T267I, E167D and E148Q in exon 2, using PCR digestion, ARMS, DGGE and/or sequencing. Mutations were detected in patients belonging to all communities, most interestingly the Maronite, Greek orthodox, Greek catholic, Syriac and Chiite communities. The most frequent mutations are M694V and V726A (27% and 20% of the total alleles respectively). M694I, E148Q and M680I mutations account respectively for 9%, 8% and 5%. Each of the K695R, E167D and F479L mutations was observed once and all the remaining mutations were not encountered. Of the alleles 33% do not carry any of the studied mutations. The mutation spectra, clinical features and severity of the disease differed among the Lebanese communities. The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations at codon 694 in exon 10 (both M694V and M694I). None of the patients carrying other mutations developed amyloidosis.

Amyloidosis↗
PubMed2001

Molecular analysis of beta-thalassemia in South Vietnam.

The high prevalence of beta-thalassemia in Southeast Asia is a major public health problem. Development of genetic counseling and prenatal diagnosis programs is a priority. To provide the groundwork for such programs in South Vietnam, we determined the spectrum of beta-thalassemia mutations in 35 severely affected patients and their relatives. We identified six different beta-thalassemia alleles (five beta(0) and one beta(+) mutations), in addition to the common mutation at codon 26 (GAG --> AAG) responsible for Hb E. These data provide insights into the distribution of beta-thalassemia alleles in the Vietnamese population.

Alleles↗