A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia

Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents'' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents'' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case.     

Efficiency and safety of oxcarbazepine in mood disorders: A naturalistic study exploring the interest of plasma dosages

OBJECTIVE: To investigate whether measurement of plasma levels can predict tolerance to oxcarbazepine (OXC). METHODS: We reviewed medical records to identify all inpatients consecutively treated by OXC at the University Department of Psychiatry in Bordeaux. Adverse effects were rated before treatment onset, at day 3, then every week and at discharge or at discontinuation. Residual hydroxy-OXC concentrations were measured on blood samples at the same periods. RESULTS: OXC was prescribed to 20 patients with bipolar (n=18) or schizoaffective bipolar-type disorder (n=2). Reported side effects were transient and occurred mostly at the beginning of the treatment. Three patients stopped OXC because of severe cutaneous side effects. Residual hydroxy-OXC plasma levels were similar in patients with or without occurrence of side effects at all times of assessment. CONCLUSION: Our data suggest that the occurrence of severe side-effects is relatively high with OXC. Measurement of plasma OXC levels does not appear to be of interest in clinical practice since plasma concentrations are not predictive of the occurrence of side effects.     

Successful treatment of idiopathic orbital inflammation with infliximab: an alternative to conventional steroid-sparing agents

Therapy for orbital pseudotumor, also called idiopathic orbital inflammation, is nonspecific and mainly based on the use of corticosteroids. Two patients with steroid-dependent idiopathic orbital inflammation, one with myositis and the other with dacryoadenitis, and intolerant of standard steroid sparing agents (methotrexate or azathioprine), were treated with infliximab, a monoclonal antitumor necrosis factor alpha antibody. In both patients, orbital manifestations disappeared following treatment. After follow-up for at least 20 months, the 2 patients still receiving infliximab remained event free. Infliximab enabled steroid tapering to less than 5 mg per day, suggesting that infliximab could constitute an alternative to conventional steroid sparing agents.     

Mantle cell lymphoma-like lymphomas in c-myc-3'RR/p53+/- mice and c-myc-3'RR/Cdk4R24C mice: differential oncogenic mechanisms but similar cellular origin

Mantle cell lymphoma (MCL) is a malignant lymphoproliferative B-cell disorder that does not occur spontaneously in mice but experimental mice model have been developed. Recently two different mice models prone to develop MCL-like lymphomas were generated: c-myc-3'RR/Cdk4(R24C) mice and c-myc-3'RR/p53+/- mice. Comparison of their gene expression profiles does not highlight specific differences other than those in relation with their specific mutational status (i.e., Cdk4(R24C) mutation or p53 mutations). We propose that similarly to typical human MCL and its blastoid or cyclin-D1 variants that correspond to the same genetic entity, MCL-like lymphomas of c-myc-3'RR/ p53+/- mice and c-myc-3'RR/Cdk4(R24C) mice represent a spectrum of the same entity.     

Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism

Hereditary forms of iron-deficiency anemia, including animal models, have taught us much about the normal physiologic control of iron metabolism. However, the discovery of new informative mutants is limited by the natural mutation frequency. To address this limitation, we have developed a screen for heritable abnormalities of red blood cell morphology in mice with single-nucleotide changes induced by the chemical mutagen ethylnitrosourea (ENU). We now describe the first strain, fragile-red, with hypochromic microcytic anemia resulting from a Y228H substitution in the ferrireductase Steap3 (Steap3(Y288H)). Analysis of the Steap3(Y288H) mutant identifies a conserved motif required for targeting Steap3 to internal compartments and highlights how phenotypic screens linked to mutagenesis can identify new functional variants in erythropoiesis and ascribe function to previously unidentified motifs.     

La filiation adoptive à l’épreuve du traumatisme

Introduction

In recent years, in order to respect the principles of the 1993 Hague Convention, international adoption has focused on children with “special needs”. These children are difficult to adopt because of their personal situation or their state of health. International adoption leads adoptive parents to move to a foreign country with unknown language, customs, culture and administrative formalities, leading to a feeling of loss of control, placing them in a vulnerable position. Some international adoptions cause real suffering for both the adopted child and his/her parents, especially when trauma disrupts the filiation process.