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Rapid extraction of temporal and spatial patterns from repeated experience is known as statistical learning (SL). Studies on SL show that after a few minutes of exposure, observers exhibit knowledge of regularities hidden in a sequence or array of objects. Previous findings suggest that SL might relate to numerical processing mechanisms. Hence, the current study examines for the first time SL in a population with a deficiency in the numerical system: individuals with mathematical learning difficulties (MLD). The results revealed that SL was significantly worse in the MLD group than in a control group. In addition, whereas the control group showed reliable SL above chance, the MLD group did not. Because learned regularities can broadly facilitate cognitive processing, individuals with MLD may thus suffer from additional behavioral challenges beyond their numerical difficulties.

Myotilinopathies are a group of muscle disorders caused by mutations in the MYOT gene. It was first described in two families suffering from limb girdle muscle dystrophy type 1 (LGMD 1A), and later identified in a subset of dominant or sporadic patients suffering from myofibrillar myopathy, as well as in a family with spheroid body myopathy. Disease phenotypes associated with MYOT mutations are clinically heterogeneous and include pure LGMD forms as well as late-onset distal myopathies. We report here on a 53-year-old male suffering from a unique clinical profile characterized by generalized symmetrical increase in muscle bulk leading to a Herculean appearance. Muscle weakness and stiffness in the lower extremities were the patient's main complaints. Muscle MRI showed extensive fatty infiltration in the thigh and leg muscles and a muscle biopsy showed a myofibrillar myopathy with prominent protein aggregates. Gene sequencing revealed a Ser55Phe missense mutation in the myotilin gene. The mutation was identified in his older brother, who presented a mild hypertrophic appearance and had a myopathic pattern in EMG, despite not presenting any of the complaints of the proband and having normal muscle strength. This finding, and his deceased father and paternal aunt's similar gait disorders, suggest that this is in fact a new autosomal dominant kindred. The present observations further expand the spectrum of clinical manifestations associated with mutations in the myotilin gene.

Desminopathy represents a subgroup of myofibrillar myopathies caused by mutations in the desmin gene. Three novel disease-associated mutations in the desmin gene were identified in unrelated Spanish families affected by cardioskeletal myopathy. A selective pattern of muscle involvement, which differed from that observed in myofibrillar myopathy resulting from mutations in the myotilin gene, was observed in each of the three families with novel mutations and each of three desminopathy patients with known desmin mutations. Prominent joint retractions at the ankles and characteristic nasal speech were observed early in the course of illness. These findings suggest that muscle imaging in combination with routine clinical and pathological examination may be helpful in distinguishing desminopathy from other forms of myofibrillar myopathy and ordering appropriate molecular investigations.

Several desmin mutations have been described over the past few years in patients with dilated and restrictive cardiomyopathy, often in association with distal myopathy. However, the role of desmin mutations as a cause of various types of cardiomyopathy is still undetermined. The aim of this study was to analyse the frequency of desmin mutations in patients with cardiomyopathy identified and diagnosed in the St. Petersburg area of Russia. We screened 98 patients with dilated, 40 with hypertrophic and 4 with restrictive cardiomyopathy. All exons of the desmin gene were amplified by PCR and studied by sequencing. Two out of 98 patients showed the presence of desmin gene mutations, not previously described in dilated cardiomyopathy. A novel IVS2-2A--G splice site mutation, presumably causing skipping of exon 3, was detected in a case of familial right ventricular dilated cardiomyopathy. An A213V mutation was associated with a case of late onset dilated cardiomyopathy. No desmin mutations were found in patients with hypertrophic or restrictive cardiomyopathy. Desmin mutations should be considered a relatively rare cause of dilated cardiomyopathy in this specific geographic area.

The spinocerebellar ataxias are a group of debilitating neurodegenerative diseases for which a clinical classification system has proved unreliable. We have recently isolated the gene for spinocerebellar ataxia type 1 (SCA1) and have shown that the disease is caused by an expanded, unstable, CAG trinucleotide repeat within an expressed gene. Normal alleles have a size range of 19-36 repeats, while SCA1 alleles have 42-81 repeats. In this study, we examined the frequency and variability of the SCA1 repeat expansion in 87 kindreds with diverse ethnic backgrounds and dominantly inherited ataxia. All nine families for which linkage to the SCA1 region of 6p had previously been established showed repeat expansion, while 3 of the remaining 78 showed a similar abnormality. For 113 patients from the families with repeat expansion, inverse correlations between CAG repeat size and both age at onset and disease duration were observed. Repeat size accounted for 66% of the variation in age at onset in these patients. After correction for repeat size, interfamilial differences in age at onset remained significant, suggesting that additional genetic factors affect the expression of the SCA1 gene product.