SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is the most common single-gene lethal disorder. Substantial patient-patient variability in disease onset and progression and response to glucocorticoids is seen, suggesting genetic or environmental modifiers. METHODS: Two DMD cohorts were used as test and validation groups to define genetic modifiers: a Padova longitudinal cohort (n = 106) and the Cooperative International Neuromuscular Research Group (CINRG) cross-sectional natural history cohort (n = 156). Single nucleotide polymorphisms to be genotyped were selected from mRNA profiling in patients with severe vs mild DMD, and genome-wide association studies in metabolism and polymorphisms influencing muscle phenotypes in normal volunteers were studied. RESULTS: Effects on both disease progression and response to glucocorticoids were observed with polymorphism rs28357094 in the gene promoter of SPP1 (osteopontin). The G allele (dominant model; 35% of subjects) was associated with more rapid progression (Padova cohort log rank p = 0.003), and 12%-19% less grip strength (CINRG cohort p = 0.0003). CONCLUSIONS: Osteopontin genotype is a genetic modifier of disease severity in Duchenne dystrophy. Inclusion of genotype data as a covariate or in inclusion criteria in DMD clinical trials would reduce intersubject variance, and increase sensitivity of the trials, particularly in older subjects.

A fully electronic sensor for the measurement of cDNA hybridization kinetics.

Ion sensitive field effect transistors (ISFET) are candidates for a new generation of fully electrical DNA sensors. To this purpose, we have modified ISFET sensors by adsorbing on their Si(3)N(4) surface poly-L-lysine and single (as well as double) stranded DNA. Once coupled to an accurate model of the oppositely charged layers adsorbed on the surface, the proposed sensor allows quantitatively evaluating the adsorbed molecules densities, as well as estimating DNA hybridization kinetics.

[Biological diagnosis of whooping cough: contribution of gene amplification]. / Diagnostic biologique de la coqueluche: apport de l'amplification génique.

An upsurge in pertussis infections, despite mandatory vaccination in France since 1966, has occurred again in developed countries due to progressive loss of vaccinal immunity and wider circulation of the causal bacterium, Bordetella pertussis. Unfortunately, the classical culture method is insufficiently sensitive and serology can only confirm diagnosis retrospectively. New techniques are needed for rapid diagnosis, and subsequent treatment and preventive measures. One new method, gene amplification using polymerase chain reaction (PCR), has been particularly useful in detecting Bordetella pertussis. PCR is highly specific and more sensitive than culture. It is thus quite useful in case of atypical clinical presentations and in previously treated or vaccinated patients. Less restrictions on sample transportation and preservation make PCR a technique which general practitioners can use for rapid easy diagnosis of pertussis.

[Haemophilus influenzae meningitis following vaccination. Consequence or coincidence?]. / Méningite à Haemophilus influenzae dans les suites d'une vaccination. Conséquence ou coïncidence?

BACKGROUND: The introduction of vaccines against Haemophilus influenzae type b (Hib) has had a substantial impact on Hib infections. Their use has established their excellent safety profiles but occasional adverse effects have been reported. CASE REPORT: A 4 month-old infant was admitted for a severe form of Hib meningitis with septicemia whose first manifestations developed 3 hours after the first immunization with a conjugate vaccine against Hib (PRP-T). The outcome was good without any sequelae. DISCUSSION: A dramatic decrease in serum antibodies due to antigen-antibody reaction during the first days after immunization has been reported; this mechanism and some epidemiological data could favor the hypothesis that the vaccine is responsible for the infection, at least the unconjugated vaccines. CONCLUSION: Any fever occurring in the immediate post-immunization period must alert the possibility of a Hib infection.

[Persistence of fetal circulation and high frequency oscillation]. / Persistance de la circulation foetale et oscillation à haute fréquence.

High frequency ventilation (HVF) was used in 17 newborns with severe respiratory distress due to persistent fetal circulation. All patients except one had been treated previously but not satisfactorily by conventional ventilation. Four children died from neurological causes despite respiratory improvement. HVF failed in one case. Twelve newborns recovered without any sequelae. Thus HVF appears to be a most valuable ventilation technique in this situation.