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Unraveling the genetics of distal hereditary motor neuronopathies.
Neuromolecular Med. 2006; 8(1-2):131-46.NM

Abstract

The hereditary motor neuronopathies (HMN [MIM 158590]) are a heterogeneous group of disorders characterized by an exclusive involvement of the motor part of the peripheral nervous system. They are usually subdivided in proximal HMN, i.e., the classical spinal muscular atrophy syndromes and distal hereditary motor neuronopathies (distal HMN) that clinically resemble Charcot-Marie-Tooth syndromes. In this review, we concentrate on distal HMN. The distal HMN are clinically and genetically heterogeneous and were initially subdivided in seven subtypes according to mode of inheritance, age at onset, and clinical evolution. Recent studies have shown that these subtypes are still heterogeneous at the molecular genetic level and novel clinical and genetic entities have been delineated. Since the introduction of positional cloning, 13 chromosomal loci and seven disease-associated genes have been identified for autosomal-dominant, autosomal-recessive, and X-linked recessive distal HMN. Most of the genes involved encode protein with housekeeping functions, such as RNA processing, translation synthesis, stress response, apoptosis, and others code for proteins involved in retrograde survival. Motor neurons of the anterior horn of the spinal cord seems to be vulnerable to defects in these housekeeping proteins, likely because their large axons have higher metabolic requirements for maintenance, transport over long distances and precise connectivity. Understanding the molecular pathomechanisms for mutations in these genes that are ubiquitous expressed will help unravel the neuronal mechanisms that underlie motor neuropathies leading to denervation of distal limb muscles, and might generate new insights for future therapeutic strategies.

Authors+Show Affiliations

Peripheral Neuropathy Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

16775372

Citation

Irobi, Joy, et al. "Unraveling the Genetics of Distal Hereditary Motor Neuronopathies." Neuromolecular Medicine, vol. 8, no. 1-2, 2006, pp. 131-46.
Irobi J, Dierick I, Jordanova A, et al. Unraveling the genetics of distal hereditary motor neuronopathies. Neuromolecular Med. 2006;8(1-2):131-46.
Irobi, J., Dierick, I., Jordanova, A., Claeys, K. G., De Jonghe, P., & Timmerman, V. (2006). Unraveling the genetics of distal hereditary motor neuronopathies. Neuromolecular Medicine, 8(1-2), 131-46.
Irobi J, et al. Unraveling the Genetics of Distal Hereditary Motor Neuronopathies. Neuromolecular Med. 2006;8(1-2):131-46. PubMed PMID: 16775372.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unraveling the genetics of distal hereditary motor neuronopathies. AU - Irobi,Joy, AU - Dierick,Ines, AU - Jordanova,Albena, AU - Claeys,Kristl G, AU - De Jonghe,Peter, AU - Timmerman,Vincent, PY - 1999/11/30/received PY - 1999/11/30/revised PY - 1999/11/30/accepted PY - 2006/6/16/pubmed PY - 2007/3/16/medline PY - 2006/6/16/entrez SP - 131 EP - 46 JF - Neuromolecular medicine JO - Neuromolecular Med VL - 8 IS - 1-2 N2 - The hereditary motor neuronopathies (HMN [MIM 158590]) are a heterogeneous group of disorders characterized by an exclusive involvement of the motor part of the peripheral nervous system. They are usually subdivided in proximal HMN, i.e., the classical spinal muscular atrophy syndromes and distal hereditary motor neuronopathies (distal HMN) that clinically resemble Charcot-Marie-Tooth syndromes. In this review, we concentrate on distal HMN. The distal HMN are clinically and genetically heterogeneous and were initially subdivided in seven subtypes according to mode of inheritance, age at onset, and clinical evolution. Recent studies have shown that these subtypes are still heterogeneous at the molecular genetic level and novel clinical and genetic entities have been delineated. Since the introduction of positional cloning, 13 chromosomal loci and seven disease-associated genes have been identified for autosomal-dominant, autosomal-recessive, and X-linked recessive distal HMN. Most of the genes involved encode protein with housekeeping functions, such as RNA processing, translation synthesis, stress response, apoptosis, and others code for proteins involved in retrograde survival. Motor neurons of the anterior horn of the spinal cord seems to be vulnerable to defects in these housekeeping proteins, likely because their large axons have higher metabolic requirements for maintenance, transport over long distances and precise connectivity. Understanding the molecular pathomechanisms for mutations in these genes that are ubiquitous expressed will help unravel the neuronal mechanisms that underlie motor neuropathies leading to denervation of distal limb muscles, and might generate new insights for future therapeutic strategies. SN - 1535-1084 UR - https://www.unboundmedicine.com/medline/citation/16775372/Unraveling_the_genetics_of_distal_hereditary_motor_neuronopathies_ L2 - https://dx.doi.org/10.1385/nmm:8:1-2:131 DB - PRIME DP - Unbound Medicine ER -