Journal ArticleDOI
Genetic and clinical aspects of Charcot‐Marie‐Tooth's disease
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The prevalence of Charcot‐Marie‐Tooth's disease was studied in Western Norway, an area with several isolated districts with a population of 725,000 (1968) and the penetrance was almost complete for all three variants of CMT.Abstract:
The prevalence of Charcot-Marie-Tooth's disease (CMT) was studied in Western Norway, an area with several isolated districts with a population of 725,000 (1968). Three hereditary types were distinguished in the area: autosomal dominant CMT with an estimated prevalence of 36/100,000; X-linked recessive CMT with a prevalence of 3.6/100,000; and autosomal recessive CMT with a prevalence of 1.4/100,00. Gene frequencies were 3 · 7. 10-4, 1 · 9. 10-4, and 4 · 8. 10-4 in autosomal dominant, X-linked, and autosomal recessive CMT, respectively, while the corresponding mutation rates were 13 · 0, 5 · 5, and 3 · 5 per million gametes per generation. The penetrance was almost complete for all three variants of CMT.
Strict diagnostic criteria were followed in the selection of the 37 index cases. A family investigation was carried out with 238 subjects, during which 69 secondary cases were detected. Another 57 subjects had unspecific neuropathy (Un), which did not fit a diagnosis of CMT or other neurological disease. In the diagnosis of Un, a score system was used, with age and sex corrections based on findings in a normal population.
Generally, the most severe disease course was found in the recessive CMT types, but there was also more clinical variation, suggesting CNS involvement in some cases (upper motor neuron affection, cerebellar signs). Scoliosis and spinal ataxia were not infrequent, even in cases with autosomal dominant CMT.
The prevalence cf Un was highest in the relatives of recessive CMT cases, with a ratio of affected to normal in sibs compatible with a hypothesis of several cases of heterozygous manifestation. In the relatives of autosomal dominant CMT cases, Un prevalence was also higher than in the population, but lower in 2nd degree relatives than in 1st degree; the ratios fitted a hypothesis of polygenic Un inheritance. Significant differences were found in the score patterns of Un in the recessive CMT families and in the autosomal dominant families, suggesting their difference of origin. The reason for clustering of Un cases in autosomal dominant CMT families is obscure, since it can be only partly attributed to early manifestation of CMT. It is suggested that Un and CMT, mainly in autosomal dominant CMT, interact to form a spectrum of differing phenotypes, so explaining the problem of “transitional forms” between CMT and other hereditary nervous disorders. Recessive CMT, being a more generalized nervous disease, attains, through differing expressivity, phenotypes which vary between individual cases.read more
Citations
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Journal ArticleDOI
Population frequencies of inherited neuromuscular diseases—A world survey
TL;DR: A survey of the world literature of the population frequencies of various inherited neuromuscular diseases has been carried out, with a conservative estimate of the overall prevalence among both sexes around 286 x 10(-6).
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DNA duplication associated with Charcot-Marie-Tooth disease type 1A
James R. Lupski,Roberto Montes de Oca-Luna,Susan A. Slaugenhaupt,Liu Pentao,V Guzzetta,Barbara J. Trask,Odila Saucedo-Cardenas,David F. Barker,James M. Killian,Carlos A. Garcia,Aravinda Chakravarti,Pragna Patel +11 more
TL;DR: It is demonstrated that failure to recognize the molecular duplication can lead to misinterpretation of marker genotypes for affected individuals, identification of false recombinants, and incorrect localization of the disease locus.
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Mitochondrial Dynamics in Mammalian Health and Disease
TL;DR: Findings in the field of mitochondrial dynamics in mammalian cells and their implication in human pathologies have established mitochondrial dynamics as a consolidated area in cellular physiology.
Journal ArticleDOI
Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse.
Annachiara De Sandre-Giovannoli,Malika Chaouch,Serguei Kozlov,Jean Michel Vallat,Meriem Tazir,Nadia Kassouri,Pierre Szepetowski,Tarik Hammadouche,Antoon Vandenberghe,Colin L. Stewart,D. Grid,Nicolas Lévy +11 more
TL;DR: This report constitutes the first evidence of the recessive inheritance of a mutation that causes CMT2; additionally, it is suggested that mutations in LMNA may also be the cause of the genetically overlapping disorder CMT1B1.
Journal ArticleDOI
Hereditary motor and sensory neuropathies.
TL;DR: The recent use of pedigree linkage analysis together with recombinant DNA techniques in these disorders has finally begun to clarify this confusing group of diseases, and it is concluded that patients with Roussy-Levy syndrome actually represent extreme expressions of CMT1.
References
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