Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues.

X-linked myotubular myopathy (XLMTM), a severe congenital myopathy, is caused by mutations in the MTM1 gene located on the X chromosome. A majority of affected males die in the early postnatal period, whereas female carriers are believed to be usually asymptomatic. Nevertheless, several affected females have been reported.

Identification of an in vivo orally active dual-binding protein-protein interaction inhibitor targeting TNFα through combined in silico/in vitro/in vivo screening.

TNFα is a homotrimeric pro-inflammatory cytokine, whose direct targeting by protein biotherapies has been an undeniable success for the treatment of chronic inflammatory diseases. Despite many efforts, no orally active drug targeting TNFα has been identified so far. In the present work, we identified through combined in silico/in vitro/in vivo approaches a TNFα direct inhibitor, compound 1, displaying nanomolar and micromolar range bindings to TNFα.

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations.

Background: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown.

Clinical and electrophysiological features in a French family presenting with seipinopathy.

Seipinopathies are a group of inherited diseases affecting upper and lower motor neurons due to mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2). We report a French family carrying the N88S mutation in the BSCL2 gene. A 12-yr-old girl complained of bilateral asymmetrical pes cavus with right hand motor deficit and amyotrophy, asymmetrical leg amyotrophy and pyramidal signs.

Type I interferon potentiates T-cell receptor mediated induction of IL-10-producing CD4⁺ T cells.

Type I interferons (IFNs) have the dual ability to promote the development of the immune response and exert an anti-inflammatory activity. We analyzed the integrated effect of IFN-α, TCR signal strength, and CD28 costimulation on human CD4⁺ T-cell differentiation into cell subsets producing the anti- and proinflammatory cytokines IL-10 and IFN-γ. We show that IFN-α boosted TCR-induced IL-10 expression in activated peripheral CD45RA⁺CD4⁺ T cells and in whole blood cultures.

Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2.

Background: Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development. Several genes have been associated with EOEE and a molecular diagnosis workup is challenging since similar phenotypes are associated with mutations in different genes and since mutations in one given gene can be associated with very different phenotypes. Recently, de novo mutations in KCNQ2, have been found in about 10% of EOEE patients.

Palmo-Plantar hyperkeratosis, intellectual disability, and spastic paraplegia in two maternal half brothers: further evidence for an X-linked inheritance.

In 1983, Fitzsimmons et al. reported four brothers with an unrecognized disorder characterized by intellectual disability, spastic paraplegia, and palmo-plantar hyperkeratosis (OMIM 309500). In this report, we describe a family in which two males, maternal half-brothers, had learning disabilities.

Ring 14 chromosome presenting as early-onset isolated partial epilepsy.

We report four infants (two males, two females) with ring 14 chromosome presenting with early-onset partial epilepsy. The first seizure occurred between 3 and 6 months (3, 3, 4, and 6mo respectively). In all four cases, diagnosis was based on early focal seizures, rather than on psychomotor retardation or morphological features, which were not prominent at seizure onset.

Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait.