We describe the clinical, hematologic and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from six families carried a
...mutation, five had the recurrent p.Arg352His mutation and one had a new deletion at the exon 7-intron 7 junction. Forty-nine families carried a
mutation, which was a known recurrent mutation in only one-third of the cases and private sequence variation in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation with liver iron content assessed by magnetic resonance imaging.
-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In
-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a 'Gardos channelopathy'. These data on the largest series to date indicate that
-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of
-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.
Mutations in the
gene, located on the X chromosome, have been recently detected in males with a transient form of antenatal Bartter syndrome or with idiopathic polyhydramnios. The aim of this study ...is to analyze the proportion of the population with mutations in this gene in a French cohort of patients with antenatal Bartter syndrome.
The French cohort of patients with antenatal Bartter syndrome encompasses 171 families. Mutations in genes responsible for types 1-4 have been detected in 75% of cases. In patients without identified genetic cause (
=42), transient antenatal Bartter syndrome was reported in 12 cases. We analyzed the
gene in the entire cohort of negative cases by Sanger sequencing and retrospectively collected clinical data regarding pregnancy as well as the postnatal outcome for positive cases.
We detected mutations in
in 17 patients, including the 12 with transient antenatal Bartter syndrome, from 16 families. Fifteen different mutations were detected (one whole deletion, three frameshift, three splicing, three nonsense, two inframe deletions, and three missense); 13 of these mutations had not been previously described. Interestingly, two patients are females; in one of these patients our data are consistent with selective inactivation of chromosome X explaining the severity. The phenotypic presentation in our patients was variable and less severe than that of the originally described cases.
mutations explained 9% of cases of antenatal Bartter syndrome in a French cohort, and accounted for 38% of patients without other characterized mutations and for 44% of male probands of negative cases. Our study confirmed previously published data and showed that females can be affected. As a result, this gene must be included in the screening of the most severe clinical form of Bartter syndrome.
Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0SMN1/1SMN2 genotype, the most severe genotype compatible ...with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset.
The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype.
SMA patients with the 0SMN1/1SMN2 genotype were retrospectively collected using the UMD-SMN1 France database.
Data from 16 patients were reviewed. These 16 patients displayed type 0 SMA. At birth, a vast majority had profound hypotonia, severe muscle weakness, severe respiratory distress, and cranial nerves involvement (inability to suck/swallow, facial muscles weakness). They showed characteristics of fetal akinesia deformation sequence and congenital heart defects. Recurrent episodes of bradycardia were observed. Death occurred within the first month. At prenatal stage, decreased fetal movements were frequently reported, mostly only by mothers, in late stages of pregnancy; increased nuchal translucency was reported in about half of the cases; congenital heart defects, abnormal amniotic fluid volume, or joint contractures were occasionally reported.
Despite a prenatal onset attested by severity at birth and signs of fetal akinesia deformation sequence, prenatal manifestations of type 0 SMA are not specific and not constant. As illustrated by the frequent association with congenital heart defects, type 0 SMA physiopathology is not restricted to motor neuron, highlighting that SMN function is critical for organogenesis.
Des syndicalistes fondent en mars 1942, après les bombardements anglais des usines Renault, un organisme humanitaire sous l’égide des nazis. Ceux-ci financent généreusement jusqu’en 1945 cet ...organisme collaborationniste pluraliste dominé par le Rassemblement national populaire (RNP) et le Parti populaire français (PPF), au moyen d’une amende sur les « fortunes juives ». Paré à la fois de la tradition ouvrière et de l’action l’humanitaire, le Comité ouvrier de secours immédiat (COSI) fustige sans relâche les « crimes anglosaxons », étale la générosité allemande et contourne le Secours national vichyste. Par-delà une aide concrète aux victimes des raids alliés qui se multiplient, le COSI s’avère un lieu majeur de corruption du syndicalisme que l’épuration frappera peu.
In March 1942, in the aftermath of the English bombing of the Renault factories, French trade unionists founded a humanitarian organisation under the aegis of the Nazi government. Up through 1945, the latter generously funded the pluralist (though largely dominated by the National Populist Rally and the French Popular Party) and collaborationist organisation’s operations by means of a fine on “wealthy Jewish families”. Armed with the tools of both working-class traditions and humanitarian activism, the Comité ouvrier de secours immédiat (COSI) relentlessly castigated “Anglo-Saxon crimes”, highlighted German generosity and circumvented the Secours national (National Emergency Relief) service established by the Vichy Regime. In this article, we argue that the COSI, far from merely offering practical assistance and relief to the growing victims of the Allies’ raids, was also a major site of syndicalist corruption scarcely touched by previous purges.
Des syndicalistes fondent en mars 1942, après les bombardements anglais des usines Renault, un organisme humanitaire sous l’égide des nazis. Ceux-ci financent généreusement jusqu’en 1945 cet ...organisme collaborationniste pluraliste dominé par le Rassemblement national populaire (RNP) et le Parti populaire français (PPF), au moyen d’une amende sur les « fortunes juives ». Paré à la fois de la tradition ouvrière et de l’action l’humanitaire, le Comité ouvrier de secours immédiat (COSI) fustige sans relâche les « crimes anglo-saxons », étale la générosité allemande et contourne le Secours national vichyste. Par-delà une aide concrète aux victimes des raids alliés qui se multiplient, le COSI s’avère un lieu majeur de corruption du syndicalisme que l’épuration frappera peu.
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