Biomedical subjects

Mena Scavina

Publications and source records attributed to Mena Scavina.

6 recordsLinked to original sources

PubMed2005

Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin-induced cell death.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in the telomeric copy of the survival motor neuron (SMN1) gene. Although the SMN protein has been implicated in the biogenesis of ribonucleoprotein complexes and RNA processing, it is not clear how these functions contribute to the pathogenesis of SMA. To gain a further understanding of SMN function, we have investigated its role in cell survival in skin fibroblasts derived from SMA patients and age-matched controls. SMA fibroblasts exposed to camptothecin, a specific inhibitor of DNA topoisomerase I, consistently showed cell death at a lower concentration than normal controls. Treatment with other cell death-inducing agents did not cause differences in survival of SMA fibroblasts as compared with control fibroblasts. Camptothecin treatment resulted in activation of caspase-3 with generation of the caspase-3 cleavage product, poly ADP-ribose polymerase (PARP). Depletion of SMN protein by RNA interference in control fibroblasts increased caspase-3 activity, whereas transfection of SMA fibroblasts with wild-type SMN decreased caspase-3 activity. Our data demonstrate that SMA fibroblasts are more prone to some, but not all, death-stimuli. Vulnerability to death-stimuli is associated with decreased levels of SMN protein and is mediated by activation of caspase-3.

Atrophy↗

PubMed2004

Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1.

OBJECTIVE: To study the NKX2-1 gene in two half-siblings with elevated thyroid-stimulating hormone (TSH) on state screen, prolonged neonatal respiratory distress despite term gestations, and persistent ataxia, dysarthria, and developmental delay. STUDY DESIGN: We amplified and sequenced DNA samples from blood or buccal swab for subjects and their unaffected siblings. RESULTS: The same mutation that prevents splicing together of exons 2 and 3 of the NKX2-1 gene was present in the affected siblings, their mother, and maternal grandmother but not in their unaffected siblings. The mutation was present in the heterozygous form, thus explaining the disease phenotype. CONCLUSIONS: Autosomal dominant transmission of mutations of NKX2-1 may cause congenital hypothyroidism, neonatal respiratory distress at term, and persistent neurologic findings such as ataxia, choreoathetosis, and dysarthria in families with affected subjects in multiple generations.

Ataxia↗

PubMed2002

Charcot-Marie-Tooth disease and related neuropathies: mutation distribution and genotype-phenotype correlation.

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disorder that has been associated with alterations of several proteins: peripheral myelin protein 22, myelin protein zero, connexin 32, early growth response factor 2, periaxin, myotubularin related protein 2, N-myc downstream regulated gene 1 product, neurofilament light chain, and kinesin 1B. To determine the frequency of mutations in these genes among patients with CMT or a related peripheral neuropathy, we identified 153 unrelated patients who enrolled prior to the availability of clinical testing, 79 had a 17p12 duplication (CMT1A duplication), 11 a connexin 32 mutation, 5 a myelin protein zero mutation, 5 a peripheral myelin protein 22 mutation, 1 an early growth response factor 2 mutation, 1 a periaxin mutation, 0 a myotubularin related protein 2 mutation, 1 a neurofilament light chain mutation, and 50 had no identifiable mutation; the N-myc downstream regulated gene 1 and the kinesin 1B gene were not screened for mutations. In the process of screening the above cohort of patients as well as other patients for CMT-causative mutations, we identified several previously unreported mutant alleles: two for connexin 32, three for myelin protein zero, and two for peripheral myelin protein 22. The peripheral myelin protein 22 mutation W28R was associated with CMT1 and profound deafness. One patient with a CMT2 clinical phenotype had three myelin protein zero mutations (I89N+V92M+I162M). Because one-third of the mutations we report arose de novo and thereby caused chronic sporadic neuropathy, we conclude that molecular diagnosis is a necessary adjunct for clinical diagnosis and management of inherited and sporadic neuropathy.

Adolescent↗

PubMedDate not supplied

Correction of cavovarus foot deformity in Charcot-Marie-Tooth disease.

Operative correction of cavovarus foot deformity in Charcot-Marie-Tooth disease (CMT) is challenging. This progressive peripheral sensory and motor neuropathy commonly involves the forefoot, midfoot, hindfoot, and toes. The authors present a new imaging technique that allows the surgeon to assess the flexibility of the hindfoot in patients with CMT to determine the best operative procedure to correct the deformity. Twenty-five patients (41 feet) with CMT and cavovarus foot deformity were evaluated and a new radiographic technique was studied in some of these patients to determine the usefulness of this imaging modality. The authors believe that this new imaging method will aid in determining the optimal operation for correcting this complex deformity.

Adolescent↗

PubMedDate not supplied

Prevalence of Charcot-Marie-Tooth disease in patients who have bilateral cavovarus feet.

It is not uncommon to see a patient with bilateral cavovarus feet in the outpatient setting. A large percentage of these patients are subsequently diagnosed with an associated condition, such as Charcot-Marie-Tooth disease. The purpose of the present report was to determine the prevalence of Charcot-Marie-Tooth disease in children who have bilateral cavovarus feet. A chart review of children with bilateral cavovarus feet was done. Patients were excluded if they had an existing medical problem known to be associated with bilateral cavovarus feet. Charcot-Marie-Tooth disease was diagnosed after a clinical assessment by an orthopaedic surgeon and a neurologist. The diagnosis was confirmed by either standard nerve conduction velocity studies and/or the CMT DNA Duplication Detection Test (Athena Diagnostics Inc, Worchester, MA). A positive family history was noted only if the diagnosis had been confirmed by a nerve conduction velocity study and/or CMT DNA Duplication Detection Test. One hundred forty-eight patients met the study criteria. The probability of a patient with bilateral cavovarus feet being diagnosed with Charcot-Marie-Tooth disease, regardless of family history, was 78% (116 patients). A family history of Charcot-Marie-Tooth disease increased the probability to 91%. It is recommended that all patients with bilateral cavovarus feet, especially with a known family history, be investigated for Charcot-Marie-Tooth disease.

Adolescent↗

PubMedDate not supplied

Passive exoskeletons for assisting limb movement.

This article presents the state of the art in passive devices for enhancing limb movement in people with neuromuscular disabilities. Both upper- and lower-limb projects and devices are described. Special emphasis is placed on a passive functional upper-limb orthosis called the Wilmington Robotic Exoskeleton (WREX). The development and testing of the WREX with children with limited arm strength are described. The exoskeleton has two links and 4 degrees of freedom. It uses linear elastic elements that balance the effects of gravity in three dimensions. The experiences of five children with arthrogryposis who used the WREX are described.

Adolescent↗