Guest guest Posted April 28, 2009 Report Share Posted April 28, 2009 PMP22 and Myelin ANN Poster Session Seattle Tuesday, April 28, 2009 4:00 PM [s15.002] Clinical and Schwann Cell Phenotypes in a Patient with PMP22 Homozygous Null Mutation Istvan K. Katona, A. Saporta, Louise Carr, Fiona Macdonald, Louise Brueton, Ueli Suter, E. Shy, M. Reilly, Jun Li, Helen P. Roper, Zurich, Switzerland, London, United Kingdom, Detroit, MI, Birmingham, United Kingdom OBJECTIVE: To determine the molecular function of PMP22 in human peripheral myelin by evaluating clinically, physiologically and morphologically a patient with a homozygous deletion of chromosome 17p11.2 BACKGROUND: PMP22 is a structural protein of the peripheral myelin with unknown function. Heterozygous deletion of chromosome 17p11.2, containing PMP22, causes hereditary neuropathy with liability to pressure palsies (HNPP). While important information has been learned from patients with HNPP, biological functions of PMP22 in humans are largely unexplored due to the rarity of patients with PMP22 null mutation. DESIGN/METHODS: A 7 year old boy with a homozygous deletion of chromosome 17p11.2 was evaluated clinically, by neurophysiology, and by punch skin biopsy. RESULTS: At 4 months of age the patient was described as a floppy infant. Motor milestones were delayed. At seven years of age, weakness was only mild in intrinsic hand muscles. In contrast, large fiber sensory modalities were profoundly abnormal and the patient required a frame due to sensory ataxia. Nerve conduction velocities were slow. A glabrous skin biopsy revealed onion bulb -like structures in the dermal nerves. Striking redundant basal lamina from Schwann cells was observed within the onion bulbs. A similar redundancy of basal lamina was seen in homozygous pmp22 null-mice where they were hypothesized to result from a loss of interaction between Pmp22 and 6 4-integrin. Immunohystochemistry with MBP antibody shows many Schwann cells lining up along axons, but failing to form mature internodes, suggesting impaired or incomplete differentiation of myelinating Schwann cells. CONCLUSIONS/RELEVANCE: Our results demonstrate that PMP22 is necessary for basal lamina organization and the maturation of myelinating Schwann cells. Without PMP22 Schwann cells cannot form mature myelinated internodes. These results suggest that myelinating Schwann cells without PMP22 are arrested at an immature stage, which we are working to characterize. The reasons for the predominant sensory phenotype of our patient are unclear. Supported by: This study is supported by the Muscular Dystrophy Association and the NIH. Quote Link to comment Share on other sites More sharing options...
Recommended Posts
Join the conversation
You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.