1,720,984 research outputs found
Hereditary motor-sensory neuropathy (HMSN) type v of late onset
No full textWe describe a dominant disease affecting 18 members in three generations. Most patients were classified either as Charcot-Marie-Tooth or Strumpell-Lorraine diseases. The index patient was a 47 years old female who presented pes cavus, bilateral cramps at lower limbs, distal muscle atrophy and rapid progression. An EMG showed signs of neurogenic atrophy but deep tendon reflexes were increased. At 60 years, the patient had painful cramps and a muscle biopsy showed neurogenic denervation. SPECT showed hyporeaction in rolandic area. One sister, at 50 years had both distal atrophy, pes cavus and spastic paraparesis. EMG showed normal conduction velocities. All known linkage for Charcot-Marie-Tooth type la, Ib, Ic, and CMTX were negative. Also the disease did not map with CMT Ha, üb, nor with CMT FVa, FVb. Therefore this is a rare family whose gene location is still unknown
Proximal spinal muscular atrophy in children and young people. Clinical and genetic contribution based on 20 cases
No full textThe authors report the genetic features the clinical evolution and the histochemical data of ten patients with intermediate spinal muscular atrophy (aged from five to fourteen years) and of ten patients with juvenile spinal muscular atrophy (aged from eleven to thirty-four years.) The AA point out the lack of a net clinical and genetic distinction between these two diseases. In the same sibship both acute case and intermediate case of infantile muscular atrophy are described. In a patient with Kugelberg-Welander disease, we had to exclude a myotonic syndrome as differential diagnosis. Large type grouping and predominance of type II fibers were found in the most benign juvenile spinal muscular atrophy
Genetic epidemiology of myotonic dystrophy
No full textPrevalence rate of myotonic dystrophy (DM) was estimated in a large sample of the Italian population. Segregation analysis of the affected families suggests that subjects showing minor clinical signs, even in the absence of myotonic features, should be considered as bearers of the DM trait. An apparent excess of normal sibs among the offspring of DM subjects may be due to the late onset of the disease and possibly to a partial loss of affected individuals from the sample before diagnosis. Prevalence rate of DM in this study is estimated between 69 to 90 per million inhabitants; accordingly, DM might be the most frequent inherited neuromuscular disorder in human populations. Copyright © 1987 Wiley-Liss, Inc., A Wiley Compan
A 3' consensus splice mutation in the human dystrophin gene detected by a screening for intra-exonic deletions
No full textMyotonic dystrophy: A disease model of disorders with dynamic mutation
No full textWe correlated the myotonic dystrophy (DM) phenotype with the degree of [CTG](n) expansion in leukocytes and skeletal muscle in our patients. Analyzing our families we found often the anticipation phenomenon and clinical severity in family members correlated with [CTG](n) expansion. We have used a muscular disability scale (MDRS) and divided our series of DM patients in 3 phenotypic classes: minimal DM in old age, juvenile/adult DM and early child-hood DM. The distribution of the [CTG](n) expansions in leukocytes was analysed for each phenotype class and was found to have a log normal curve. Our results can be used to derive a prognostic index for each phenotypic class, although individual variations may be attributed to somatic mosaicism in different tissues, i.e. larger [CTG](n) expansions in skeletal muscle and other stable tissues. The ability of [CTG](n) mutation to alter the accumulation of poly (A) + RNA in trans in muscle tissue suggests that MD may be an example of a dominant negative mutation manifested at the RNA level. The expression of the DM-PK gene has been explored in skeletal muscle tissue: in muscle there is a selective expression at DM-PK gene product in type 1 fibers. We have observed biochemical and histochemical changes consistent with an altered modulatory mechanism of sarcoplasmic reticulum that may result in myotonia and atrophy of type 1 fibers and concurrent 'slow to fast' transformation. While this may explain the muscle alterations much remains to be studied to understand the multisystemic expression of this disorder
A novel missense mutation in the L1CAM gene in a boy with L1-disease.
No full textA novel missense mutation of the L1CAM gene (Xq28) is described in an adult patient affected with severe mental retardation, spastic paraparesis, adducted thumbs, agenesis of corpus callosum and microcephaly (L1 disease). We detected a transition c2308G-->A in exon 18 that caused an amino acid change in codon 770. The patient's mother and two sisters were heterozygous for the same mutation. This newly described mutation predicts the substitution of an aspartate by asparagine (D770N) in the second fibronectin (Fn2) domain of the extracellular portion of the mature L1 protein. Even if amino acid substitution does not significantly change the physico-chemical properties of the Fn2 domain, it seems clear that the integrity of this domain is required to maintain the biological functions of the protein. The feature peculiar to this patient is the decelerated head growth post-natally, leading to microcephaly. Mutations of L1CAM associated with prolonged survival may hamper post-natal brain and head growth
Facioscapulohumeral muscular dystrophy: epidemiological and molecular study in a north-east Italian population sample.
No full textFacioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease associated with a partial deletion on chromosome 4q35. Few relevant investigations have been reported on its epidemiology and were essentially based on clinical diagnosis, having been performed before recognition of the molecular mutation. We report an epidemiological survey on FSHD patients, in which the diagnosis was obtained by combined clinical and molecular evaluation. The survey concerned the north-east Italian province of Padova, an area of 871,190 inhabitants (1 January 2004). We identified 40 patients affected by FSHD based on clinical diagnosis. In 33 of them, the EcoRI fragment size in the 4q35 region ranged from 14 to 35 kb. Four other patients belonging to the same family harbored a 38-kb fragment. In these four cases, the relationship between the borderline deletion with the mild FSHD phenotype was corroborated by additional haplotype reconstruction and segregation analysis. Interestingly, the same mild facial-sparing clinical pattern was apparent only in one other patient with an EcoRI fragment of 32 kb, suggesting that this unusual FSHD phenotype may be due to very small 4q35 deletions. On the whole, estimating a prevalence rate of 44 x 10(-6), our survey confirmed FSHD as one of the most frequent neuromuscular disorders in Western populations
Sporadic cases in Duchenne muscular dystrophy. A reappraisal through segregation analysis on 988 sibships
No full textA new estimation of the proportion of sporadic cases in Duchenne muscular dystrophy was attempted by means of segregation analysis in a sample of 988 sibships collected on a world-wide scale by different authors. Maximum likelihood estimates of ascertainment probability (π), segregation frequency (p), and frequency of sporadic cases (x) were calculated by Morton's equations under different hypotheses. The best fit was found for p=0.454±0.024 and x=0.235±0.034. The possibility that the proportion of sporadic cases might be lower than the expected 1/3 is suggested. © 1987 Springer-Verlag
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