Clinical and molecular diagnosis of spinal muscular atrophy.
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The spinal muscular atrophies are a group of disorders characterized by flaccid limb weakness. It is necessary to differentiate these from other causes and identify the SMA variants. In classical SMA, majority of the patients shows homozygous deletion of the telomeric SMN gene (SMN1) on chromosome 5q. The availability of DNA analysis has allowed proper genetic counseling and prenatal diagnosis in the affected families. Application of newer techniques has enabled more accurate carrier detection. Our objective is to stress the variability in the clinical features and recent advances in the molecular diagnosis for SMA. (+info)
Involvement of survival motor neuron (SMN) protein in cell death.
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Infantile spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron (SMN)1 gene. We investigated the role of human (h) SMN protein on cell death in PC12 and Rat-1 cells. hSMN prolonged cell survival in PC12 cells deprived of trophic support and in Rat-1 cells induced to die by activation of the proto-oncogene c-Myc, to similar magnitude as Bcl-2 or IAP-2. While hSMN was ineffective in inhibiting apoptosis induced by ultraviolet light (UV) or etoposide treatment in proliferating PC12 or Rat-1 cells, a protective effect was observed in terminally NGF/dBcAMP-differentiated PC12 cells. hSMN inhibited the onset of apoptosis in NGF/dBcAMP-deprived or UV-treated co-differentiated PC12 cells by preventing cytochrome c release and caspase-3 activation, indicating that its effects are through suppression of the mitochondrial apoptotic pathway. Expressing hSMN deleted for exon 7 (Delta7) or for exons 6 and 7 (Delta6/7), or with the SMA point mutant Y272C, resulted in loss of survival function. Moreover, these mutants also exhibited pro-apoptotic effects in Rat-1 cells. The localization pattern of full-length hSMN in PC12 and Rat-1 cells was similar to that of endogenous SMN: granular labelling in the cytoplasm and discrete fluorescence spots in the nucleus, some of which co-localized with p80 coilin, the characteristic marker of Cajal bodies. However, cytoplasmic and nuclear aggregates were often seen with hSMNDelta7, whereas the hSMNDelta6/7 mutant showed homogenous nuclear labelling that excluded the nucleolus. Thus, our results show that the C-terminal region is critical in suppression of apoptosis by SMN. (+info)
Postoperative use of a cough-assist device in avoiding prolonged intubation.
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Postoperative management following major surgery in patients with neuromuscular disorders associated with scoliosis is frequently complicated by sputum retention and ventilatory failure. This report demonstrates the successful perioperative management of an 11-yr-old boy with type II spinal muscular atrophy undergoing a single-stage posterior spinal fusion procedure. Use of an MI-E device was able to successfully treat sputum retention and avoid a tracheostomy. (+info)
Use of power mobility for a young child with spinal muscular atrophy.
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BACKGROUND AND PURPOSE: Young children with severe motor impairments, such as spinal muscular atrophy, are often unable to move around their environment independently; therefore, they may be at risk for delays in areas of development not directly related to their motor limitations. Power mobility is an intervention that provides young children a means of independent movement and enables them to independently explore their environment. CASE DESCRIPTION: The participant was a 20-month-old girl with type II spinal muscular atrophy. INTERVENTION: The authors provided the child with a power wheelchair and gave her mother and physical therapist general guidelines to encourage her use of the power wheelchair. OUTCOMES: Within 6 weeks after receiving the power wheelchair, the child operated the wheelchair independently. She showed developmental gains in all domains of the Battelle Developmental Inventory and the Pediatric Evaluation of Disability Inventory over 6 months. The authors conducted an interview with the child's mother before and after intervention. She reported that the child was more independent after receiving the power wheelchair. DISCUSSION: The power wheelchair may have been associated with the changes in the child's mobility and her developmental changes over 6 months. (+info)
Genetic diagnosis of Werdnig-Hoffmann disease: a problem for application to prenatal diagnosis.
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We report a floppy infant with Werdnig-Hoffmann disease (spinal muscular atrophy: SMA type 1) and Klinefelter syndrome. After genetic counseling with parents, a genetic diagnosis using DNA from the infant's peripheral blood mononuclear cells was performed. The parents' deletion of exons 7 and 8 of the survival motor neuron (smn) gene and exons 4 and 5 of the neuronal apoptosis inhibitory protein (naip) gene were noted in the infant, so he was confirmed to have SMA type 1. The parents wanted to receive a prenatal diagnosis on the next pregnancy. However this genetic test is achieved by confirming that a specific band can not be detected by PCR. Therefore, this method should be applied with great care to prenatal diagnosis using chorionic villi, which may be contaminated with maternal tissue. (+info)
Molecular genetic analyses of five Vietnamese patients with spinal muscular atrophy.
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Most patients with spinal muscular atrophy (SMA) have been reported to show homozygous deletion of the gene responsible for SMA, SMN1. However, whether SMA patients homozygous for the SMN1 deletion exist in Southeast Asian countries, including Vietnam, remains to be determined, because molecular genetic analyses of SMA patients from these countries have not been reported. In this preliminary study, we analyzed five Vietnamese SMA patients and found that SMN1 gene exons 7 and 8 were completely absent in one of them, a 6-month-old girl with hypotonic muscles. Thus, SMN1 deletion can be a cause of SMA in Vietnam, although other genetic abnormalities should be considered as etiological factors in many cases. In conclusion, we identified a homozygous deletion of the SMN1 gene in a Vietnamese SMA patient. Since the number of the patients analyzed in this study was very limited, it is too early to determine whether SMN1 deletion is not a main cause of SMA in Vietnam. (+info)
Peripheral and segmental spinal abnormalities of median and ulnar somatosensory evoked potentials in Hirayama's disease.
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OBJECTIVES: To investigate the origin of juvenile muscle atrophy of the upper limbs (Hirayama's disease, a type of cervical myelopathy of unknown origin). SUBJECTS: Eight male patients were studied; data from 10 normal men were used as control. METHODS: Median and ulnar nerve somatosensory evoked potentials (SEP) were recorded. Brachial plexus potentials at Erb's point (EP), dorsal horn responses (N13), and subcortical (P14) and cortical potentials (N20) were evaluated. Tibial nerve SEP and motor evoked potentials (MEP) were also recorded from scalp and spinal sites to assess posterior column and pyramidal tract conduction, respectively. RESULTS: The most important SEP findings were: a very substantial attenuation of both the EP potentials and the N13 spinal responses; normal amplitude of the scalp N20; and normal latency of the individual peaks (EP-N9-N13-P14-N20). Although both nerves were involved, abnormalities in response to median nerve stimulation were more significant than those in response to ulnar nerve stimulation. There was little correlation between the degree of alterations observed and the clinical state. Latencies of both spinal and cortical potentials were normal following tibial nerve stimulation. The mean latency of cervical MEP and the central conduction time from the thenar eminence were slightly but significantly longer in patients than in controls. CONCLUSIONS: The findings support the hypothesis that this disease, which is clinically defined as a focal spinal muscle atrophy of the upper limb, may also involve the sensory system; if traumatic injury caused by stretching plays a role in the pathogenesis, the damage cannot be confined to the anterior horn of the spinal cord. (+info)
Spinal Muscular atrophy (SMA) Type I is a fatal autosomal recessive disease caused by homozygous deletion of telometric region of exon 7/8 of the SMN gene. Prenatal diagnosis is feasible and desirable by most families. We report on prenatal diagnosis of SMAI in a family where dried umbilical cord stump from the deceased affected baby was used to confirm the diagnosis. Prenatal diagnosis was provided in the subsequent pregnancy. We emphasize the need for storing DNA from individuals affected with suspected single gene disorders. (+info)