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Biomedical subjects

B Hainque

Publications and source records attributed to B Hainque.

At least 19 recordsLinked to original sources
PubMed2006

Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss.

OBJECTIVE: To investigate the mRNA expression of adiponectin, AdipoR1 and AdipoR2, the two recently cloned adiponectin receptors and peroxisome proliferator activated receptor (PPAR)gamma2 in adipose tissue of obese individuals before and during a very low calorie diet (VLCD) inducing weight loss. METHODS: Twenty-three non-diabetic obese subjects with normal (NGT, n = 11) or impaired glucose tolerance (IGT, n = 12) (age, 47 +/- 3 years; body mass index, 39.3 +/- 1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet daily without exercise. mRNA levels of nine IGT and six NGT subjects were measured by real-time PCR in s.c. abdominal adipose tissue. RESULTS: Metabolic parameters and insulin sensitivity were improved by VLCD in the IGT group, but minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the IGT (P = 0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARgamma2 mRNA levels did not change during VLCD in any group. In the IGT, but not in the NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of PPARgamma2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively related to each other and to that of adiponectin. CONCLUSION: In the NGT group, the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin sensitivity and the expression of the adiponectin system in adipose tissue. By contrast, in the IGT group, AdipoR1 expression increased and we found a coordinate regulation of the expression of adiponectin and its receptors. These modifications could participate, through adiponectin action on adipocytes, to the improved metabolic parameters observed in IGT subjects.

Adipose Tissue↗
PubMed2005

[X-linked adrenoleukodystrophy in a female proband: clinical presentation, biological diagnosis and family consequences].

INTRODUCTION: X-linked adrenoleukodystrophy (ALD) is the most frequent type of leukodystrophy (1/17 000 males). The phenotypic range in male patients varies from the severe cerebral presentations in children to the milder myeloneuropathy and to isolate adrenal insufficiency. More than a half of the carrier females display clinical symptoms over the age of 40 years. OBSERVATION: Diagnosis of ALD was raised in a 40 year-old female who presented with spastic paraparesis and sphincterian dysfunction, occurring after the delivery of her first child. There was no family history of ALD. Very long-chain fatty acids (VLFCA) were assayed in her one-year-old son in order to propose appropriate hormonal and neurological survey. His dosage was abnormal and an adrenal insufficiency was subsequently found. A brain MRI will be proposed biannually when he reaches to age of for years. The proband's mother had an increased level of VLCFA, showing that she was a carrier. Family screening was extended to the proband's sisters and maternal aunt who already had children, but also to her brother, who may express a mild form of the disease later on, and to her maternal uncles who might be asymptomatic carriers. A frameshift mutation was found in the ABCD1 gene and will allow accurate carrier identification and prenatal diagnosis in the family. CONCLUSION: ALD diagnosis should be evoked in a woman affected by myelopathy despite the lack of family history. Such a diagnosis has severe consequences since some of the related males may carry the mutation although they do not display any symptom at time of diagnosis, and because carrier females have a risk to both have a clinical expression of the disease and give birth to an affected boy.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed2004

New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis.

BACKGROUND: Periodic paralysis is classified into hypokalemic (hypoPP) and hyperkalemic (hyperPP) periodic paralysis according to variations of blood potassium levels during attacks. OBJECTIVE: To describe new mutations in the muscle sodium channel gene SCN4A that cause periodic paralysis. METHODS: A thorough clinical, electrophysiologic, and molecular study was performed of four unrelated families who presented with periodic paralysis. RESULTS: The nine affected members had episodes of muscle weakness reminiscent of both hyperPP and hypoPP. A provocative test with potassium chloride was positive in two patients. However, repeated and carefully performed tests of blood potassium levels during attacks resulted in normal potassium levels. Remarkably, two patients experienced hypokalemic episodes of paralysis related to peculiar provocative factors (corticosteroids and thyrotoxicosis). Similarly to hyperPP, electromyography in nine patients revealed increased compound muscle action potentials after short exercise and a delayed decline during rest after long exercise as well as myotonic discharges in one patient. With use of molecular genetic analysis of the gene SCN4A, three new mutations were found affecting codon 675. They resulted in an amino acid substitution of a highly conserved arginine (R) to either a glycine (G), a glutamine (Q), or a tryptophan (W). Interestingly, hypoPP is caused by both mutations affecting nearby codons as well as the change of an arginine into another amino acid. CONCLUSION: A potassium-sensitive and normokalemic type of periodic paralysis caused by new SCN4A mutations at codon 675 is reported.

Acetazolamide↗
PubMed2004

Low incidence of cardiac events with beta-blocking therapy in children with long QT syndrome.

AIMS: To evaluate the effect of beta-blockers in children with long QT syndrome (LQTS) we reviewed the outcome of 122 patients (pts). METHODS: LQTS was diagnosed in 24 neonates and in 98 pts aged 0.5-15 years. Diagnosis was made because of syncope in 51 pts, bradycardia in 10 neonates and family history in 61 pts. The longest QTc ranged from 400 to 700 ms. Thirteen pts had 2:1 atrioventricular block and/or ventricular arrhythmias. Screening for mutations was performed in 118 pts. All children were treated with beta-blockers, annually checked by exercise testing and/or 24 h ECG monitoring. RESULTS: Four pts died. Survivors were followed-up for 1-18 years (7.5 +/- 5.3 years). Five neonates and 3 older pts received a prophylactic pacemaker (1 death) so that only 111/122 pts survived and were followed-up with beta-blockers alone. None of them died and five experienced a non-fatal cardiac event. There was no cardiac event among pts who were diagnosed because of familial history and among symptomatic KCNQ1 pts who were effectively treated with beta-blockers. CONCLUSION: The outcome of children with LQTS under effective beta-blockers is favourable. Persisting arrhythmia or symptoms despite beta-blockers should aim at identifying other genotypes than KCNQ1.

Adolescent↗
PubMed2004

Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women.

OBJECTIVE: We assessed the relationships between four circulating acute phase proteins and the circulating and adipose tissue levels of three adipocytokines. SUBJECTS: In all, 15 nondiabetic obese women with a body mass index (BMI) above 32 kg/m(2) were investigated. METHOD: Circulating concentrations of C-reactive protein (CRP), alpha 1 acid glycoprotein (AAG), fibrinogen, alpha 1 antitrypsin and both circulating and adipose tissue levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha and leptin were measured by either nephelometry or enzyme-linked immunosorbent assay. RESULTS: We found a strong positive correlation between both circulating and adipose tissue levels of IL-6, TNFalpha and leptin and serum CRP levels. All these adipose tissue adipocytokines were also positively correlated with serum AAG levels. These correlations disappeared when adjusted for fat mass, suggesting that the relationship observed was dependent on fat amount. CONCLUSION: Our results indicate a strong relationship between adipocytokines and inflammatory markers, and suggest that cytokines secreted by adipose tissue in obese subjects could play a role in increased inflammatory proteins secretion by the liver.

Acute-Phase Proteins↗
PubMed2004

[Neonatal forms of congenital long QT syndrome].

UNLABELLED: The neonatal congenital long QT syndrome (LQTS) is rare and of bad prognosis due to the presence of severe ventricular arrhythmia and conduction abnormalities. METHODS: we included 24 propositus newborns from our population with LQTS. Genetic study was possible in 19 cases. RESULTS: the diagnosis of LQTS was made according to a QT prolongation associated with a sinusal neonatal bradycardia (n=9) or a 2/1 AV block (n=15). The onset presentation consisted of syncope (n=2), torsades de pointes (n=7), cardiovascular collapse (n=5), cardiac arrest (n=1). The mean QTc was at 550+60 ms. During the neonatal period the treatment consisted of beta-blocking agents in all cases, associated with a definitive pacemaker implantation in 10 cases with 2/1 AV block. Three newborns with a 2/1 AV block died during the first month of life (one case due to a septecemia after implantation of a pacemaker, and two who were waiting for that implantation). All survivors remained asymptomatic during a follow-up period of 7 years. In all cases with a 2/1 AV block we identified mutations in HERG (n=8). Newborns with isolated sinusal bradycardia presented all a mutation in KCNQ1 (n=9). CONCLUSION: the LTQS with 2/1 AV block is preferably associated with mutation in HERO with a bad initial prognosis.

Female↗
PubMed2003

Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis.

A missense variant (R83H) of the gene (KCNE3) encoding a potassium channel-associated peptide, MinK-related peptide 2 (MiRP2), has been reported in periodic paralysis patients. In the current study, no difference in the frequency of the MiRP2-R83H variant between periodic paralysis patients and healthy individuals was found. Furthermore, there was no segregation of this gene variant with the disease. These observations weaken the proposal that MiRP2-R83H causes periodic paralysis.

Adult↗
PubMed2003

Interpretation of circulating C-reactive protein levels in adults: body mass index and gender are a must.

OBJECTIVE: The recently demonstrated association between C-reactive protein (CRP) level and body mass index (BMI) raised the question of the link between CRP and the degree of obesity. In the present study, we measured CRP in a healthy population with a wide range of BMI in order to appreciate the influence of overweight in the interpretation of CRP results in clinical use. METHOD: Blood donors, aged from 19 to 65 years, were included in the study. According to BMI, subjects were classified into 3 groups: A (BMI<25 kg/m(2), n=611); B (25-30, n=147); C (> 30, n=34). RESULTS: CRP values were different among women and men. CRP progressively increased with BMI in women. These results clearly showed that average level of CRP was quite different according to BMI and gender of the subjects and generated different normal ranges of CRP expressed in mg/L (median, 75(th) percentile): Group A: women: 0.44, 0.93; men: 0.40, 0.79, Group B: women: 1.28, 1.84; men: 0.84, 2.17, Group C: women: 3.61, 7.21; men: 1.16, 3.08. CONCLUSION: Our results suggest that for an inflammatory disease diagnosis, a CRP concentration of 5 mg/L is normal for obese women but is five times the 75(th) percentile for normal people.

Adult↗
PubMed2002

Genetic testing and genetic counselling in hypertrophic cardiomyopathy: the French experience.

AIMS: A major breakthrough in the molecular genetics of hypertrophic cardiomyopathy (HCM) has made genetic testing now available in clinical practice, raising new questions about its implications, potential benefits, and the organisation of the procedure. The aim of this work was (1) to discuss the different questions related to genetic testing in HCM, and propose guidelines for the different situations, (2) to report our preliminary experience with a specific procedure. METHODS AND RESULTS: The main questions asked by patients and relatives concern presymptomatic diagnosis and prenatal counselling/diagnosis, while clinicians sometimes discuss diagnostic and prognostic testing. To take into account the complex medical and psychological implications of this new approach, we developed a specific, multidisciplinary, and multiple step procedure, including a cardiologist, a geneticist, and a psychologist. Seventy subjects were examined, including (1) 29 adults for presymptomatic diagnosis (of whom 10 left the procedure after the first visit and 19 continued, among whom six had a mutation and two experienced negative psychological impact, observed during follow up), (2) nine couples of parents for presymptomatic diagnosis in their children (the procedure was stopped after the first visit in eight and continued in one), (3) 22 couples for prenatal counselling (no prenatal genetic testing was asked for after the first visit), and (4) 10 subjects for diagnostic testing. We decided to perform no prognostic testing. CONCLUSION: Our preliminary experience confirms the complexity of the situation and suggests the necessity for a specific procedure to ensure good practice in genetic testing of HCM.

Adolescent↗
PubMed2001

Notched T waves on Holter recordings enhance detection of patients with LQt2 (HERG) mutations.

BACKGROUND: The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potassium channels, are the most common cause of the dominant long-QT syndrome (LQTS). In addition to QT-interval prolongation, notched T waves have been proposed as a phenotypic marker of LQTS patients. METHODS AND RESULTS: The T-wave morphology of carriers of mutations in KCNQ1 (n=133) or HERG (n=57) and of 100 control subjects was analyzed from Holter ECG recordings. Averaged T-wave templates were obtained at different cycle lengths, and potential notched T waves were classified as grade 1 (G1) in case of a bulge at or below the horizontal, whatever the amplitude, and as grade 2 (G2) in case of a protuberance above the horizontal. The highest grade obtained from a template defined the notch category of the subject. T-wave morphology was normal in the majority of LQT1 and control subjects compared with LQT2 (92%, 96%, and 19%, respectively, P:<0.001). G1 notches were relatively more frequent in LQT2 (18% versus 8% [LQT1] and 4% [control], P:<0.01), and G2 notches were seen exclusively in LQT2 (63%). Predictors for G2 were young age, missense mutations, and core domain mutations in HERG. CONCLUSIONS: This study provides novel evidence that Holter recording analysis is superior to the 12-lead ECG in detecting G1 and G2 T-wave notches. These repolarization abnormalities are more indicative of LQT2 versus LQT1, with G2 notches being most specific and often reflecting HERG core domain missense mutations.

Adult↗
PubMed2001

Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A.

Hypokalaemic periodic paralysis (hypoPP) is an autosomal dominant muscle disorder characterized by episodic attacks of muscle weakness associated with a decrease in blood potassium levels. Mutations in the gene encoding the skeletal muscle voltage-gated calcium channel alpha-1 subunit (CACNL1A3) account for the majority of cases. Recently, mutations in the gene coding for the skeletal muscle voltage-gated sodium channel alpha subunit (SCN4A) have been reported in a small number of hypoPP families. In order to determine the relative frequency of the CANCL1A3 and SCN4A mutations in a large population of hypoPP patients, and to specify the clinical and pathological features associated with each of them, we searched for mutations in 58 independent hypoPP index cases. We detected the causative mutation in 45 cases: 40 were linked to the CACNL1A3 gene and five to the SCN4A gene. One mutation has not been described before. Some remarkable clinical features were observed in a large hypoPP family carrying an SCN4A mutation: a complete penetrance in men and women, an early age at onset, postcritic myalgias and an increased number and severity of attacks induced by acetazolamide. A muscle biopsy, performed in two members of this family, revealed a peculiar myopathy characterized by tubular aggregates. In contrast, vacuoles were predominant in muscles from hypoPP patients carrying CACNL1A3 mutations. Our findings point to the usefulness of a molecular characterization of hypoPP patients in clinical practice. They also provide new clues for understanding the mechanisms behind functional and structural alterations of the skeletal muscle in hypoPP.

Adolescent↗
PubMed2001

[T wave abnormalities on Holter monitoring of congenital long QT syndrome: phenotypic marker of a mutation of LQT2 (HERG)].

The two genes which code for the potassium channels, KCNQ1 and HERG, are responsible for the most common forms of the long QT syndrome, LQT1 and LQT2. Abnormalities of duration and morphology of the ventricular repolarisation are amongst the diagnostic criteria of this syndrome. The morphology of the T waves was studied by 24 hour Holter monitoring in 190 subjects with a long QT syndrome due to KCNQ1 (LQT1) [N = 133] or HERG (N = 57) and in 100 controls, and it was compared with the ECG T wave. The T wave was characterised according to 3 morphological features: grade 0 (G0) = normal, grade 1 (G&) = slight ST depression and grade 2 (G2) = presence of ST elevation of the descending phase of the T wave. The T wave morphology on Holter ECG was normal for most LQT1 and control subjects compared with LQT2 (92%, 96% and 19% respectively, p < 0.01). Grade 1 appearances were observed more often in LQT2 (18 vs 8% for LQT1 and 4% for controls, p < 0.01). Grade 2 appearances were only observed in the cases of LQT2 (63%). The predictive factors of G2 were young age and an anti-sense mutation of the transmembrane domaines of HERG. The authors conclude that Holter monitoring improves detection of T wave changes compared with the ECG. Grade 2 changes seem to be a phenotype marker for a HERG mutation, especially those situated in the transmembrane domaines.

Adolescent↗
PubMed2000

Deletion in the cardiac troponin I gene in a family from northern Sweden with hypertrophic cardiomyopathy.

The cardiac troponin I gene has been described to be associated with hypertrophic cardiomyopathy. Until now, mutations in this gene have been found only in the Japanese population. We now present the first non-Japanese family, from northern Sweden, with a mutation in the cardiac troponin I gene. Clinical diagnose was based on echocardiography, with a maximum left ventricular wall thickness of >13 mm, or major electrocardiographic abnormalities, excluding subjects with other known causes of cardiac hypertrophy. Mutation screening was performed with a single-strand conformation polymorphism analysis and identification of mutation by direct DNA sequencing. We have identified a 33-bp deletion in exon 8 encompassing the stop codon. Nine individuals in three generations were tested, and four were carriers of this deletion. The mother was genetically affected and died of heart failure aged 90. Echocardiography at 71 years of age revealed no hypertrophy, but the electrocardiogram showed signs of left ventricular hypertrophy. Her two sons, also genetically affected, had left ventricular hypertrophy, with maximum wall thickness of 15 and 16 mm, respectively. One daughter and four grandchildren were clinically unaffected, but one of them, a 27-year-old woman with maximum wall thickness of 8 mm and normal electrocardiogram, was found to be genetically affected. In conclusion, we describe a non-Japanese family in which hypertrophic cardiomyopathy is due to a genetic defect in the cardiac troponin I gene. This mutation is a deletion of 33 bp in the last exon, whereas the previously described mutations in this gene are single nucleotide changes and a single codon deletion. The deletion of the C-terminal part of the cardiac troponin I protein, seems in this particular family to be associated with a mild phenotypic expression of familial hypertrophic cardiomyopathy.

Adult↗
PubMed2000

Homozygotes for a R869G mutation in the beta -myosin heavy chain gene have a severe form of familial hypertrophic cardiomyopathy.

UNLABELLED: Familial Hypertrophic Cardiomyopathy (FHC) is an autosomal dominant disease characterised by ventricular hypertrophy, with predominant involvement of the interventricular septum. It is a monogenic disease with a high level of genetic heterogeneity (nine genes and more than 110 mutations reported so far). We describe a family with a new R869G mutation in the beta -myosin heavy chain gene (MYH7). This mutation was found in the heterozygous status in both parents and in the homozygous status in the two children. A haplotype analysis on the MYH7 locus with microsatellite markers showed that the same haplotype is transmitted within the family, suggesting a founder effect. Clinically, the father was asymptomatic with mild left ventricular hypertrophy on echocardiography. The mother had a mild form of hypertrophic cardiomyopathy and remained asymptomatic until 60 years old when an atrial fibrillation occurred. For the two children, clinical diagnosis was performed at 12 and 8 years and atrial fibrillation occurred at 17 years. For both children, the evolution was characterized by left ventricle (LV) systolic dysfunction and a severe dilatation of the left atrium before 40 years of age. CONCLUSIONS: In this family, a new R869G mutation in the MYH7 gene was found. Interestingly, a mutation was found at the homozygous status for the first time in FHC. This finding suggests that this particular mutation is compatible with life, but for homozygous subjects, age at onset of symptoms was earlier and the disease much more severe than in the heterozygous subjects, suggesting a gene-dose effect.

Adult↗