Two cases of benign neuromyelitis optica in patients with celiac disease.

Neuromyelitis optica (NMO) is an autoimmune inflammatory disorder of the central nervous system, which predominately affects optic nerves and spinal cord. Celiac disease (CD) or gluten sensitivity is an autoimmune enteropathy triggered by ingestion of wheat gliadin and related proteins in genetically susceptible individuals. Although NMO is associated with other autoimmune disorders in around 30% of cases, an association of NMO with CD has rarely been reported. We describe two Caucasian women who, nineteen and two years after diagnosis of CD, respectively, had recurrent episodes of myelitis and optic neuritis consistent with the diagnosis of NMO. Despite numerous relapses, NMO followed an unusually mild course with no persistent neurological deficit, indicating that recurrent NMO can follow a benign course with complete remission. We discuss in detail a possible link between NMO and pre-existing CD.

Transcriptional activation of the non-muscle, full-length dystrophin isoforms in Duchenne muscular dystrophy skeletal muscle.

Despite promoter tissue specificity, up-regulation of the brain and Purkinje cell type dystrophin isoforms was described in skeletal muscle of X-linked dilated cardiomyopathy (XLDCM) and BMD affected individuals. An extended population of 11 Duchenne muscular dystrophy (DMD) and 11 Becker muscular dystrophy (BMD) patients was investigated to determine whether ectopic muscle expression of the two full-length non-muscular isoforms is a common event in dystrophinopathies and if it has functional significance. Up-regulation of the two non-muscle-specific isoforms was detected in four DMD patients but in none of the BMD affected individuals or non-dystrophic controls. This is the first report of an expression of these two isoforms in DMD skeletal muscle. Ectopic expression is not confined to regenerating or revertant fibers and does not correlate with age at biopsy, clinical phenotype, cardiac involvement, deletion size or location. We consider that muscle ectopic expression of the brain and Purkinje cell-type isoforms has no favorable prognostic significance in DMD and BMD patients.

Loss of Dp140 dystrophin isoform and intellectual impairment in Duchenne dystrophy.

BACKGROUND: Mental retardation is a clinical feature of Duchenne dystrophy (DD) and affects about one-third of patients. No clear association has been found between DNA mutations, protein expression, and IQ scores, although distal deletions in the dystrophin gene have been reported in association with intellectual impairment. A role for the brain distal dystrophin isoform Dp140 was suggested. OBJECTIVE: To explore the possible association between cognitive impairment and DNA macrodeletions in the distal part of the gene, including Dp140 gene region. METHODS: Sixty-six patients with DD received general intelligence assessment by Wechsler Intelligence Scales measuring full, verbal, and performance IQ. PCR analysis was performed to detect deletions in the dystrophin gene, and the Dp140 regulatory region was analyzed in a subgroup of 12 patients. Statistical analysis was performed by nonparametric Wilcoxon rank signed and rank sum tests. RESULTS: Comparison of neuropsychological and genetic data revealed an association between distal macrodeletions and cognitive impairment (p < 0.001). Comparing deletions involving the Dp140 gene region with deletions presumably not altering Dp140 expression resulted in even greater significance. CONCLUSIONS: These data suggest that in DD, distal dystrophin deletions are associated with intellectual impairment. This study highlights a possible role for the brain distal isoform Dp140 in normal cognitive development.

Loss of Dp140 regulatory sequences is associated with cognitive impairment in dystrophinopathies.

Mental retardation is a clinical feature present in both Duchenne and Becker muscular dystrophy patients and its pathogenesis is still unknown. Dp140 is a dystrophin isoform with predominant expression during foetal brain development. Its promoter and first exon lie in the large intron between exon 44 and 45, a region that is commonly deleted in dystrophinopathic patients. We performed neuropsychological evaluation and genetic analysis of the Dp140 transcription unit on 12 Duchenne muscular dystrophy and 28 Becker muscular dystrophy patients carrying deletions in this critical region. Comparison of neuropsychological and molecular data showed that there is a statistically significant relationship between the loss of Dp140 transcription unit and mental retardation in Becker muscular dystrophy patients (P = 0.008). Such a correlation is not evident in Duchenne muscular dystrophy patients but only shows a trend towards significance (P = 0.063). It is worth noting that both Duchenne muscular dystrophy and Becker muscular dystrophy patients with normal intelligence do not show deletions in the Dp140 regulatory regions. In the light of these findings, we suggest that impairment of cognitive abilities in Duchenne muscular dystrophy and Becker muscular dystrophy patients might be related to a dysfunction of Dp140 brain isoform.

Sarcoglycan deficiency in a large Italian population of myopathic patients.

Autosomal recessive limb-girdle muscular dystrophies are a heterogeneous group of genetic diseases with a wide spectrum of clinical severity and age of onset; mutations in the gene encoding the dystrophin-associated sarcoglycan proteins (alpha, beta, gamma and delta) have recently been shown to cause some cases of these myopathies (primary sarcoglycanopathies, types 2D, 2E, 2C and 2F, respectively). In this study we have examined a large population of Italian myopathic patients to determine the frequency of (alpha-, beta- and gamma-sarcoglycan deficiency and to correlate molecular defects with clinical phenotypes; to exclude the presence of primary dystrophinopathies both genetic and immunological analysis of dystrophin was performed. We report 12 patients (10 male and 2 female) with deficiency of either one or more sarcoglycan proteins. They were aged 8-56 years with onset between 4 and 30 years of age; they all presented with either mild, moderate or severe limb-girdle involvement associated with elevated blood creatine kinase levels and myopathic pattern at EMG; one was also affected with a mild dilation cardiomyopathy. All patients, except one, showed pathological muscle histological changes. Absence of all three proteins always correlates with severe forms, whereas mild protein deficiencies or isolated partial alpha-sarcoglycan deficiency correlate with either severe, moderate or mild forms.

[The determination of serum amino-terminal procollagen type-III propeptide (PIIINP) in occupational exposure to rock wool fiber]. / Il dosaggio del propeptide aminoterminale del procollagene III sierico (PIIINP) nell'esposizione professionale a fibre di lana di roccia.

Fifty-six males workers exposed to rock wool during production, and 20 referents were examined. Exposure, evaluated by personal sampling, ranged from 0.05 to 0.74 fibres/ml (median 0.15). The subjects underwent a medical examination, chest X-ray according to ILO recommendations and pulmonary function tests. In all subjects the serum levels of type III procollagen N-terminal propeptide (PIIINPs) were determined. No evidence of pulmonary fibrosis, nor work-related lung diseases were observed. PIIINPs mean values in the exposed (9.8 ng/ml; 2.8 S.D.) were slightly higher, but not significantly different when compared to referents (8.5 ng/ml; 2.5 S.D.). No significant correlation between PIIINPs and rock wool exposure (both airborne levels and exposure duration) was observed. Furthermore, peptide levels were not related to pulmonary function test results. Our results suggest that occupational exposure to rock wool fibres lower than 0.75 fibres/ml for less than 20 years does not induce definite cases of pulmonary fibrosis nor an increase of type III collagen synthesis in the lung.

[A case of pleuro-pulmonary asbestosis in a distillery worker engaged in clarification of alcohols with asbestos]. / Su di un caso di asbestosi pleuro-polmonare in addetto alla chiarificazione di alcoolici in distilleria.

The Authors report a case of pleuro-pulmonary asbestosis with concurrent dermatological findings. Work hazard is very peculiar: the subject has worked in distilleries for 45 years, till 1962, to clear and filter alcohol using asbestos.