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Clinical and pathological phenotype of the original family with Charcot-Marie-Tooth type 1B: a 20-year study.
Ann Neurol. 1997 Apr; 41(4):463-9.AN

Abstract

Charcot-Marie-Tooth type 1B is an uncommon form of hereditary motor and sensory neuropathy caused by mutations in the P(0) myelin protein gene on chromosome 1. We report here a 20-year observation of 13 members of the first family with Charcot-Marie-Tooth disease to demonstrate linkage to chromosome 1 and now known to have a C270A mutation in the P(0) gene altering the extracellular domain of the protein. Affected individuals generally show an early age at onset, often indicated by delayed ability to walk. Proximal muscle weakness of the lower extremities is common and often marked, but the individuals remain ambulatory and there is no decrease in life span. Motor nerve conduction velocities of the fastest fibers are severely slowed (mean, 9-11 m/sec), even when compared with 3 families having Charcot-Marie Tooth type 1A (mean, 19-21 m/sec). Variability of disability between family members suggests that genetic and environmental factors in addition to the P(0) mutation play a role in the final phenotype. Nerve biopsy specimens demonstrate hypertrophy, onion bulb formation, loss of myelinated fibers, and occasional myelin thickening similar to that described in P(0) myelin knockout mice. Autopsy of the 92-year-old great-grandmother in this family demonstrated diffuse involvement of sensory and motor nerves, with loss of myelin in the posterior columns of the spinal cord and loss of anterior horn neurons but without other involvement of the central nervous system. This family demonstrates the long-term phenotypic consequences on the peripheral nervous system of a specific point mutation in the P(0) myelin gene.

Authors+Show Affiliations

Neurology Section, VA Medical Center, Seattle, WA 98108, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

9124803

Citation

Bird, T D., et al. "Clinical and Pathological Phenotype of the Original Family With Charcot-Marie-Tooth Type 1B: a 20-year Study." Annals of Neurology, vol. 41, no. 4, 1997, pp. 463-9.
Bird TD, Kraft GH, Lipe HP, et al. Clinical and pathological phenotype of the original family with Charcot-Marie-Tooth type 1B: a 20-year study. Ann Neurol. 1997;41(4):463-9.
Bird, T. D., Kraft, G. H., Lipe, H. P., Kenney, K. L., & Sumi, S. M. (1997). Clinical and pathological phenotype of the original family with Charcot-Marie-Tooth type 1B: a 20-year study. Annals of Neurology, 41(4), 463-9.
Bird TD, et al. Clinical and Pathological Phenotype of the Original Family With Charcot-Marie-Tooth Type 1B: a 20-year Study. Ann Neurol. 1997;41(4):463-9. PubMed PMID: 9124803.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and pathological phenotype of the original family with Charcot-Marie-Tooth type 1B: a 20-year study. AU - Bird,T D, AU - Kraft,G H, AU - Lipe,H P, AU - Kenney,K L, AU - Sumi,S M, PY - 1997/4/1/pubmed PY - 1997/4/1/medline PY - 1997/4/1/entrez SP - 463 EP - 9 JF - Annals of neurology JO - Ann. Neurol. VL - 41 IS - 4 N2 - Charcot-Marie-Tooth type 1B is an uncommon form of hereditary motor and sensory neuropathy caused by mutations in the P(0) myelin protein gene on chromosome 1. We report here a 20-year observation of 13 members of the first family with Charcot-Marie-Tooth disease to demonstrate linkage to chromosome 1 and now known to have a C270A mutation in the P(0) gene altering the extracellular domain of the protein. Affected individuals generally show an early age at onset, often indicated by delayed ability to walk. Proximal muscle weakness of the lower extremities is common and often marked, but the individuals remain ambulatory and there is no decrease in life span. Motor nerve conduction velocities of the fastest fibers are severely slowed (mean, 9-11 m/sec), even when compared with 3 families having Charcot-Marie Tooth type 1A (mean, 19-21 m/sec). Variability of disability between family members suggests that genetic and environmental factors in addition to the P(0) mutation play a role in the final phenotype. Nerve biopsy specimens demonstrate hypertrophy, onion bulb formation, loss of myelinated fibers, and occasional myelin thickening similar to that described in P(0) myelin knockout mice. Autopsy of the 92-year-old great-grandmother in this family demonstrated diffuse involvement of sensory and motor nerves, with loss of myelin in the posterior columns of the spinal cord and loss of anterior horn neurons but without other involvement of the central nervous system. This family demonstrates the long-term phenotypic consequences on the peripheral nervous system of a specific point mutation in the P(0) myelin gene. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/9124803/Clinical_and_pathological_phenotype_of_the_original_family_with_Charcot_Marie_Tooth_type_1B:_a_20_year_study_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0364-5134&date=1997&volume=41&issue=4&spage=463 DB - PRIME DP - Unbound Medicine ER -