Upload
wei-qiu
View
213
Download
0
Embed Size (px)
Citation preview
future efforts to look for role for this drug in PD should probably con-centrate on patients disabled by severe levodopa-induceddyskinesia.
doi:10.1016/j.jocn.2010.07.059
59. Epidermolysis bullosa with late-onset muscular dystrophyand plectin deficiencyEppie M. Yiu a, Alfred Klausegger b, Leigh Waddell c, Kim Tran d, C.W.Chow a, Kathryn North c, Dedee Murrell d, Monique M. Ryan a
a Royal Children’s Hospital, VICb Paracelsus Medical University, Austriac The Children’s Hospital at Westmead, NSWd St. George Hospital, NSW
Objective: Epidermolysis bullosa associated with muscular dys-trophy (EB-MD) is a rare, autosomal recessive form of epidermolysisbullosa simplex caused by mutations in PLEC1. We describe a mildcase due to compound heterozygous mutations in PLEC1,(2677del9 and the novel mutation Q1644X).
Methods: Clinical, pathological and mutation analysis findingsare described.
Results: The patient is a 40 year old male who presented withslowly progressive weakness from age 28. Clinical features includemild skin blistering since birth, late-onset upper limb predominantweakness, facial weakness, partial ptosis, incomplete ophthalmople-gia and paroxysmal atrial fibrillation. Skin immunofluorescencemapping showed significantly reduced and fragmented staining ofplectin at the dermal-epidermal basement membrane. Plectin stain-ing in muscle showed increased staining of the cytoplasm and sarco-lemma of type 1 fibres, and decreased staining of type 2 fibres.Desmin staining was significantly reduced in the sarcolemma withabnormal inclusion bodies in the cytoplasm. Mutation analysisrevealed compound heterozygosity for a novel spontaneous paternalnonsense mutation 4930C > T/Q1644X in exon 31, and a previouslyreported maternal deletion (2677del9/893del3) in exon 21. This in-frame deletion may convey a milder clinical phenotype due the pres-ence of partially functional protein. Most previous cases of EB-MDhave been due to nonsense or frame-shift mutations with down-stream premature termination codons on both alleles.
Conclusions: This is the first Australian case of EB-MD with anovel mutation in one allele. This case demonstrates a mild clinicalphenotype and highlights the unusual clinical phenotype of EB-MD.
doi:10.1016/j.jocn.2010.07.060
60. HLA-DRB1 alleles are determinants of spinal cord pathologyin Multiple Sclerosis (MS)Wei Qiu a, Sonja Raven b, Jing-Shan Wu a, Yuebei Luo a, Ian James c,William M. Carroll a, Frank L. Mastaglia a, Allan G. Kermode a
a Centre for Neuromuscular and Neurological Disorders, University ofWestern Australia, WAb Neurointerventional and Imaging Services of Western Australia, WAc Centre for Clinical Immunology & Biomedical Statistics, MurdochUniversity & Royal Perth Hospital, WA
Objective: To determine whether HLA-DRB1 alleles influencespinal cord pathology in MS.
Methods: Two hundred and fifty-two consecutive MS patientsfrom the Perth Demyelinating Disease Database had MRI scans of
the spinal cord and brain and high-resolution HLA-DRB1 genotyping.The numbers, locations, shape and segmental extent of cord lesionswere analysed and correlated with HLA-DRB1 alleles.
Results: The frequency of diffuse cord lesions was higher in HLA-DRB1*1501 carriers than non-carriers (14.0 vs 5.3%, p = 0.036, uncor-rected) and in HLA-DRB1*1501 homozygotes than heterozygotes(28.6 vs 7.9%, p = 0.01, uncorrected) with a strong dose effect. Carri-ers of HLA-DRB1*0701 had significantly more wedge-shaped lesionsthan non-carriers (71.4 vs 28.1/%, p = 0.0002, corrected) whereasHLA-DRB1*0301 carriers had fewer wedge-shaped lesions thannon-carriers (14.9 vs 41.1%, p = 0.001, uncorrected). HLA-DRB1*1104 carriers had significantly more focal lesions than non-carriers (median 7.1 vs 4.1, p = 0.002). The HLA-DRB1*0701 allelewas positively correlated with cervical lesion location while theDRB1*0401 allele was correlated with thoracic lesion location(p < 0.05).
Conclusions: Our study provides evidence that HLA-DRB1 allelesmay have a role in the development of spinal cord lesions in MS.
doi:10.1016/j.jocn.2010.07.061
61. Hypothalamic lesions and association with HLA-DRB1 allelesin Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO)Wei Qiu, Sonja Raven, Jing-Shan Wu, William M. Carroll, Frank L.Mastaglia, Allan G. Kermode
Centre for Neuromuscular and Neurological Disorders, University ofWestern Australia, WA
Objectives: To determine the frequency of hypothalamic lesionsand correlation with HLA-DRB1 alleles in West Australian patientswith MS and NMO.
Methods: Brain MRI scans of 105 Caucasian patients with classi-cal MS (50 with stable and 55 with more active disease) and 12patients with NMO were reviewed and high-resolution HLA-DRB1genotyping was performed.
Results: Hypothalamic lesions were found in 13.3% of MS patientsand in none of the NMO patients. A higher frequency of hypotha-lamic lesions was found in patients with active MS (18.2%) than inthe stable group (8.0%), but the difference was not statistically signif-icant (p = 0.13). Patients with hypothalamic lesions also had morelesions in other cerebral areas and had a significantly higher fre-quency of HLA-DRB1*0401 than patients without hypothalamiclesions (30.0 vs 5.8%, p = 0.04, uncorrected).
Conclusions: Hypothalamic lesions in MS are more frequent thanpreviously reported and may be associated with the HLA-DRB1*0401allele, but were not found in any of the NMO group of patients.
doi:10.1016/j.jocn.2010.07.062
62. Rotenone toxicity in parkin mutated olfactory cell culturesBrian Koentjoro, Alan Mackay-Sim, Carolyn M. Sue
Kolling Institute of Medical Research, NSW
Background: Mutations in Parkin have been reported to causeParkinson’s disease (PD). In addition, experimental studies haveshown that chronic systemic exposure of rotenone, a mitochondrialcomplex I inhibitor, results in the development of PD in animalmodels.
Aim: To investigate the susceptibility of human olfactory cell cul-tures with parkin mutations to rotenone exposure.
1628 Abstracts / Journal of Clinical Neuroscience 17 (2010) 1610–1638