Raeymaekers P, Timmerman V, Nelis E, De Jonghe P, Hoogendijk J E, Baas F, Barker D F, Martin J J, De Visser M, Bolhuis P A
Born-Bunge Foundation, Department of Biochemistry, University of Antwerp (UIA), Belgium.
Neuromuscul Disord. 1991;1(2):93-7. doi: 10.1016/0960-8966(91)90055-w.
Hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT 1) is an autosomal dominant disorder of the peripheral nervous system characterized by progressive weakness and atrophy of distal limb muscles. In the majority of HMSN I families, linkage studies localized the gene (CMT 1a) to the pericentromeric region of chromosome 17. We have detected with probe pVAW409R3 (D17S122) localized in 17p11.2 a duplication, co-segregating with the disease in 12 HMSN I families. In these families the duplication was present in all 128 patients but absent in the 84 unaffected and 44 married-in individuals (lod score of 58.44 at zero recombination). Further, on one HMSN I family the disease newly appeared simultaneously with a de novo duplication originating from an unequal crossing-over event at meiosis. Since different allelic combinations were found segregating with the duplication in different families linkage disequilibrium was not a significant factor. These findings led us to propose that the duplication in 17p11.2 itself is the disease causing mutation in all the HMSN I families analyzed.
遗传性运动和感觉性神经病I型（HMSN I）或夏科-马里-图斯病1型（CMT 1）是一种常染色体显性外周神经系统疾病，其特征为远端肢体肌肉进行性无力和萎缩。在大多数HMSN I家族中，连锁研究将该基因（CMT 1a）定位到17号染色体的着丝粒周围区域。我们用定位在17p11.2的探针pVAW409R3（DUT17S122）检测到一个重复片段，在12个HMSN I家族中该重复片段与疾病共分离。在这些家族中，128例患者均存在该重复片段，而84例未患病个体和44例嫁入个体中则不存在（在零重组时连锁值为58.44）。此外，在一个HMSN I家族中，疾病与减数分裂时不等交换事件产生的新生重复片段同时新出现。由于在不同家族中发现不同的等位基因组合与该重复片段共分离，所以连锁不平衡不是一个重要因素。这些发现使我们提出，17p11.2处的重复片段本身就是所有分析的HMSN I家族中的致病突变。
