Disease relevance of Hereditary Motor and Sensory Neuropathies

• We conclude that autosomal dominant HMSN VI is caused by mutations in MFN2, emphasizing the important role of mitochondrial function for both optic atrophies and peripheral neuropathies [1].
• The patients with the G-insertion showed the clinical, electrophysiological and morphological characteristics of common HNPP, but in addition they had significantly more neuropathic features, mimicking hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1) [2].
• Gene for hereditary neuropathy with liability to pressure palsies (HNPP) maps to chromosome 17 at or close to the locus for HMSN type 1 [3].
• In 5 cases showing neither duplication, deletion, nor a point mutation in the exons of the PMP-22 gene on heteroduplex DNA analysis, the histopathological findings strongly suggested a diagnosis of chronic inflammatory demyelinating polyneuropathy in 2 cases, and HMSN Ib, or HMSN non-a non-b, and HMSN III in 3 cases [4].
• Twelve affected persons in the third decade of life or later, and the 14 nearest age- and sex-matched unaffected relatives, of a large kindred with autosomal dominant hereditary motor and sensory neuropathy not linked to the Duffy blood group (HMSN type IA) were assessed for arrhythmia and cardiomyopathy [5].

High impact information on Hereditary Motor and Sensory Neuropathies

• De novo mutation of the myelin P0 gene in Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III) [6].
• Our results identify the PMP-22 gene as a likely candidate for the mouse trembler locus and will encourage the search for mutations in the corresponding human gene in pedigrees with hypertrophic neuropathies such as Charcot-Marie-Tooth and Dejerine-Sottas diseases (hereditary motor and sensory neuropathies I and III) [7].
• Autosomal recessive Charcot-Marie-Tooth disease (CMT) type 4 (CMT4) is a complex group of demyelinating hereditary motor and sensory neuropathies presenting genetic heterogeneity [8].
• We have studied eight families with HMSN I (also called the hypertrophic form of Charcot-Marie-Tooth disease) for linkage of the disease locus to polymorphic loci in the centromeric region of chromosome 17 [9].
• Hereditary motor and sensory neuropathy (HMSN) with focally folded myelin sheaths, or Charcot-Marie-Tooth type 4B (CMT4B), is a distinct clinical entity belonging to the heterogeneous group of autosomal recessive demyelinating neuropathies [10].

Chemical compound and disease context of Hereditary Motor and Sensory Neuropathies

• De novo mutation of the myelin Po gene in Déjérine-Sottas disease (hereditary motor and sensory neuropathy type III): two amino acid insertion after Asp 118 [11].
• OBJECTIVE: To report a novel hereditary motor and sensory neuropathy (HMSN) phenotype, with partial steroid responsiveness, caused by a novel dominant mutation in the myelin protein zero (MPZ) gene [12].
• The collagen fibrils that were present within the basal laminal tubes that had surrounded degenerated myelinated fibres in the diabetic nerves, and those within the onion bulbs of the HMSN cases, were of the normal endoneurial calibre [13].
• Twenty-three cases of hereditary demyelinating neuropathies are reported, 13 with different types of hereditary motor and sensory neuropathy (HMSN) and 9 with globoid cell or meta-chromatic leucodystrophies [14].
• Plasma glucosylceramide levels of 5 patients with Hereditary Motor and Sensory Neuropathy Type III (Dejerine-Sottas disease) were approximately 50% higher than in controls [15].

Biological context of Hereditary Motor and Sensory Neuropathies

• We have investigated the myelin P0 gene on chromosome 1 as a candidate gene in two sporadic cases with Dejerine-Sottas disease or hereditary motor and sensory neuropathy (HMSN) type III [6].
• Point mutations of the P0 gene cause HMSN I in a small number of families [16].
• Three genetic loci for the Charcot-Marie-Tooth (CMT) syndromes with slow motor nerve conduction velocities (hereditary motor and sensory neuropathy: HMSN type I) have been mapped to chromosomes 1 (CMT1B), 17 (CMT1A), and the X chromosome (CMTX) [17].
• Most MPZ mutations lead to the HMSN type I phenotype, with recent reports of Déjérine-Sottas, congenital hypomyelination, and HMSN II also ascribed to MPZ mutations [12].
• Molecular genetics revealed that mutations affecting the PMP22 gene are responsible for the most common forms of hereditary motor and sensory neuropathies in humans [18].

Anatomical context of Hereditary Motor and Sensory Neuropathies

• Charcot-Marie-Tooth disease (CMT), also named hereditary motor and sensory neuropathies, includes a clinically and genetically heterogeneous group of disorders affecting the peripheral nervous system [19].
• Peripheral myelin protein 22 (PMP22) is expressed by Schwann cells in the peripheral nervous system (PNS), and mutations affecting the PMP22 gene are associated with hereditary motor and sensory neuropathies [20].
• Patients with both HMSN I and the other polyneuropathies had few cells in peripheral blood and in bone marrow producing antibodies binding to P2, MAG and MBP in a solid phase immunospot assay [21].
• CMCT may be abnormal in HMSN due to central motor pathways involvement or altered spinal excitability with increased synaptic delay [22].
• The electron microscopic features and quantitative morphometric data of the sural nerve in Déjérine-Sottas disease (HMSN III) and in the hypertrophic form of Charcot-Marie-Tooth disease (HMSN I) are reported [23].

Gene context of Hereditary Motor and Sensory Neuropathies

• Mutations affecting PMP22 are associated with hereditary motor and sensory neuropathies [24].
• Probably a fourth locus (CMT1C) exists since some autosomal dominant HMSN I families have been excluded for linkage with the CMT1A and CMT1B loci [25].
• X-linked, dominant CMTX1 disease is the second most common type of these hereditary motor and sensory neuropathies (HMSN) [26].
• Because motor symptoms were prominent in these latter two kinships, the disease was designated HMSN type IIB or Charcot-Marie-Tooth type 2B (CMT2B) neuropathy [27].
• Various mutations of PO, PASII/PMP22 and connexin 32 genes were recently reported in hereditary neuropathies, such as Charcot-Marie-Tooth disease (CMT) and Dejerine Sottas disease (DS) [28].

Analytical, diagnostic and therapeutic context of Hereditary Motor and Sensory Neuropathies

• The prevalence rate is compared with previous prevalence studies focusing on Charcot-Marie-Tooth disease or hereditary motor and sensory neuropathy (HMSN) [29].
• The importance of quantitative electron microscopy in studying hypertrophic neuropathies. A comparison between a case of Déjérine Sottas disease (HMSN III) and a case of the hypertrophic form of Charcot-Marie-Tooth disease (HMSN I) [23].

References