Hentati A, Lamy C, Melki J, Zuber M, Munnich A, de Recondo J
Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-12, Hôpital des Enfants-Malades, Paris, France.
Genomics. 1992 Jan;12(1):155-7. doi: 10.1016/0888-7543(92)90419-s.
The autosomal dominant forms of hereditary motor and sensory neuropathies include the hypertrophic form (CMT1) and the neuronal form of Charcot-Marie-Tooth disease (CMT2). While at least two distinct loci have been shown to be linked to the CMT1 phenotype (CMT1A and CMT1B, on chromosomes 17 and 1, respectively), whether the CMT2 phenotype results from mutations allelic to either of the CMT1 genes remains unknown. Studying one CMT1 and two CMT2 pedigrees, we were able to exclude the CMT2 disease locus from the region of chromosome 17 (Z = -2.80 at theta = 0.05 for D17S58) where the CMT1A gene maps (Z = +3.67 at theta = 0.00). Similarly, negative lod score values were obtained in CMT2 for the region of chromosome 1 where the CMT1B gene has been located (Z = -3.09 at theta = 0.05 for D1S61). The present study therefore provides evidence for genetic heterogeneity between the hypertrophic and the neuronal forms of Charcot-Marie-Tooth disease and demonstrates that the CMT2 gene is not allelic to either of the CMT1 genes mapped to date.
遗传性运动和感觉神经病的常染色体显性遗传形式包括肥厚型（CMT1）和夏科-马里-图思病的神经元型（CMT2）。虽然至少有两个不同的基因座已被证明与CMT1表型相关（CMT1A和CMT1B，分别位于17号和1号染色体上），但CMT2表型是否由CMT1基因之一的等位基因突变引起仍不清楚。通过研究一个CMT1和两个CMT2家系，我们能够将CMT2疾病基因座排除在17号染色体区域（对于D17S58，在θ=0.05时Z=-2.80），而CMT1A基因定位于该区域（在θ=0.00时Z=+3.67）。同样，在CMT2中，对于CMT1B基因所在的1号染色体区域，获得了负对数优势分值（对于D1S61，在θ=0.05时Z=-3.09）。因此，本研究为夏科-马里-图思病的肥厚型和神经元型之间的遗传异质性提供了证据，并证明CMT2基因与迄今已定位的任何一个CMT1基因都不是等位基因。
