The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype

neurogenetics - Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy with a prevalence of 1 in 2500 individuals worldwide. Here, we report three Turkish siblings from...     

T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma.

BACKGROUND: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. OBJECTIVE: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. METHODS: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. RESULTS: The mean +/- SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P = .12). On the other hand, the mean +/- SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 +/- 0.75 vs 0.71 +/- 0.6; P = .004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean +/- SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 +/- 0.78 vs 1.65 +/- 0.55; P = .01). CONCLUSION: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.     

The influence of bilateral sagittal split ramus osteotomy on submental‐cervical aesthetics

The effect of orthodontic‐surgical treatment on submental‐cervical region was evaluated in a very limited number of studies. The aim of this study was to evaluate submental‐cervical soft tissue contour changes following mandibular advancement and set‐back procedures via bilateral sagittal split ramus osteotomy. Sixty‐seven patients were included in this study. Group 1 consisted of 27 skeletal Class II patients who underwent mandibular advancement surgery, whereas Group 2 consisted of 40 skeletal Class III patients who underwent mandibular set‐back surgery. Various linear and angular measurements were performed on pre‐operative and sixth month post‐operative cephalometric radiographs. A new method was used to evaluate the amount of sagging at submental region. The submental length did not change in Group 1; however, it decreased significantly in Group 2 (P < 0·05). The angle between submental plane and facial plane decreased to 95·9° from 98·8° in Group 1(P < 0·05), whereas it increased to 93·1° from 88·2° in Group2 (P < 0·05). The change of submental soft tissue sag was almost stable in Group 1, while 0·34 mm increase of sag was observed in Group 2. This increase was not statistically significant (P > 0·05). Mandibular set‐back and advancement procedures do not remarkably change the submental sag following approximately 6 mm jaw movement. Although mandibular advancement did not significantly effect submental length, soft tissue followed mandibular set‐back with a ratio of 1:1 at C‐point to projection of soft tissue pogonion and 1:0·7 at C‐point to soft tissue menton distances.     

Cognition of the mothers of patients with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) has been found to be associated with cognitive impairment. However, few studies have addressed cognitive impairment among mothers of children with DMD. In the present study, the neuropsychological profiles of both carrier mothers (C-Ms) and noncarrier mothers (NC-Ms) were examined, and the findings were compared with healthy control mothers (HC-Ms). There were 90 participants, consisting of 31 C-Ms, 24 NC-Ms, and 35 HC-Ms, each of whom completed a neuropsychological test battery. C-Ms had poorer cognition performance in attention, working memory, immediate verbal memory, visuospatial skills, and executive functions than NC-Ms, and HC-Ms. This study provides evidence that there may be cognitive impairment in mothers of patients with DMD. The cognitive impairment of C-Ms has similarities to that seen in children with DMD.     

The rare coexistence of high titer inhibitor development and gastrointestinal stromal tumor in a patient with severe hemophilia: A case report

Hemophilia is a hereditary disease with impaired blood coagulation due to a genetic deficiency of blood coagulation factors. The development of inhibitors further complicates the course of the disease and management. The case is here reported of a haemophilia patient who presented with coexisting development of high titer inhibitor with Gastrointestinal Stromal Tumor (GIST) diagnosis and was admitted with upper gastrointestinal system bleeding. The patient had no prior history of inhibitor presence. During all procedures including surgery, excellent hemostasis was achieved with rFVIIa treatment and no hemorrhagic complication was observed. To the best of our knowledge, this constitutes the first reported case of GIST associated with inhibitor development in a hemophilia A patient.