High prevalence of ventricular repolarization abnormalities in people carrying TGFßR2 mutations.

Mutations in the TGFßR2 gene have been associated with a life threatening risk of aortic dissection but no arrhythmic death has been previously reported. Two young females carrying a TGFßR2 mutation, initially diagnosed as Marfan syndrome or Loeys Dietz syndrome, presented sudden death with autopsy ruling out dissection. The ECGs of the 2 Sudden Cardiac Deaths revealed profound ventricular repolarization abnormalities with a sinusoidal T-U morphology associated with normal left ventricular ejection fraction. These data strongly suggest sudden cardiac arrhythmic deaths and prompted us to systematically study the repolarization pattern in the patients with TGFßR2 mutations. ECG findings from 58 mutation carriers patients (TGFßR2 group) were compared with those of 46 non-affected first degree relatives (control group). TGFßR2 mutation was associated with ventricular repolarization abnormalities in 47% of patients (p < 0.001 vs. controls), including a 19.6 ms (95%CI 8.7; 30.5) QTc interval prolongation compared to the non-affected first degree relatives (p < 0.001), higher prevalence of abnormal U waves (16% vs. 2%), and sinusoidal T-U morphology (10% vs. 0%). TGFßR2 mutations can be associated with abnormal ventricular repolarization pattern, longer QT interval than non-carrier relatives and an increased risk for sudden death.

A PCSK9 variant and familial combined hyperlipidaemia.

BACKGROUND: Our discovery in 2003 of the first mutations of PCSK9 gene causing autosomal dominant hypercholesterolaemia (ADH) shed light on an unknown factor that strongly influences the level of circulating low density lipoprotein cholesterol (LDL-C). PCSK9 gain of function mutations cause hypercholesterolaemia by a reduction of LDL receptor levels, while PCSK9 loss of function variants are associated with a reduction of LDL-C values and a decreased risk of coronary heart disease. METHODS AND RESULTS: We report an insertion of two leucines (p.L21tri also designated p.L15_L16ins2L) in the leucine stretch of the signal peptide of PCSK9 that is found in two of 25 families with familial combined hyperlipidaemia (FCHL). This mutant is associated with high total cholesterol and LDL-C values in these families and is found also in a patient with familial hypercholesterolaemia and her father. CONCLUSION: PCSK9 variants might contribute to FCHL phenotype and are to be taken into consideration in the study of this complex and multigenic disease with other genes implicated in dyslipidaemia.

Genetic heterogeneity of autosomal dominant hypercholesterolemia.

Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated elevation of plasmatic low-density lipoprotein cholesterol associated with high risk of premature cardiovascular complications. More than 1000 mutations in the LDLR gene and 9 in the APOB gene have been implicated. We have shown further heterogeneity with the discovery of missense mutations in the PCSK9 gene resulting in ADH. Different studies have tried to evaluate the respective contribution of mutations in each gene to the disease, but results were not always in agreement. After a brief overview of mutations reported for each gene, strategies and results of these different studies are reviewed and analyzed. Altogether, numerous reports give evidence for the existence of a greater level of genetic heterogeneity in ADH and the involvement of still unknown genes.

[After the LDL receptor and apolipoprotein B, autosomal dominant hypercholesterolemia reveals its third protagonist: PCSK9]. / Après le récepteur des LDL et l'apolipoprotéine B, l'hypercholestérolémie familiale révèle son troisième protagoniste: PCSK9.

The genes encoding the low-density lipoproteins receptor and its ligand apolipoprotein B, have been the only two genes classically implicated in autosomal dominant hypercholesterolemia. We have identified in 2003, the third gene implicated in this disease: PCSK9 (Proprotein Convertase Subtilin Kexin 9). Several mutations (p.S127R, p.F216L, p.D374Y...) of this gene have been reported to cause hypercholesterolemia by a gain of function leading to a reduction of LDL receptor levels. Other variations of PCSK9 are conversely associated with hypocholesterolemia particularly the non-sense p.Y142X and p.C679X mutations found in 2% of black Americans and associated with a decrease of LDL levels and coronary heart diseases. PCSK9 substrates and exact role have not been elucidated yet, but it seems that PCSK9 is definitely a major actor in cholesterol homeostasis. PCSK9 inhibitors might constitute new therapeutic targets that would decrease plasma LDL cholesterol levels and be synergistic with statin drugs.

[Dermoid cyst of the floor of the mouth. Apropos of a case and a review of the literature]. / Kyste dermoïde du plancher buccal. A propos d'un cas et revue de la littérature.

We report a large suprahyoid dermoid cyst located on the midline of the floor of the mouth. Classification, etiopathogenesis, positive and differential diagnosis, treatment, and prognosis are discussed. This anomaly is an infrequent congenital disorder that usually becomes apparent during the second or third decade of life. Prognosis is excellent after correct surgical treatment.

[Apropos of a case of infection after esthetic rhinoplasty]. / A propos d'un cas d'infection après rhinoplastie esthétique.

Infection after rhinoplasty is infrequent occurring in less than 1% of cases. When it does occur it may be due to devascularised spicule of bone or in a hematoma. Of much less frequent occurrence is the toxic shock syndrome associated or not with nasal packing and due to staphylococcus aureus. When administering prophylactic antibiotic in nasal surgery one must take into consideration their own hazards: drug reaction, candida infection or resistant staphylococcus aureus.

[Tissue losses of the heel]. / Pertes de substance de la coque talonnière.

Regional island fasciocutaneous flaps are the method of choice for the treatment of skin defects in the heel. They give good functional results with minimal esthetic sequelae.