Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)
Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)
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DOI：
10.1093/hmg/5.9.1373
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发表时间：
1996-09-01
影响因子：
3.5
通讯作者：
Ionasescu, R
中科院分区：
文献类型：
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作者：
Ionasescu, V;Searby, C;Ionasescu, R
对一个常染色体显性遗传2型夏科-玛丽-牙轴索神经病(CMT2)家系进行了临床、电生理和遗传连锁研究，共38个成员，其中14个成员受累。发病年龄16~30岁，手部软弱萎缩重于足部，12例进展缓慢。上肢深部肌腱反射消失，下肢肌腱反射减弱。触觉、本体感觉和振动感觉远端感觉手多于脚。运动神经传导速度正常值(48~53M/S)，潜伏期正常(2~3ms)，肌电有失神经征象。遗传连锁分析使用分布在22个常染色体上的167个短串联重复标记(STRP)。利用标记D7S435(在theta=0时Z=4.83)，在7p14处发现了与7号染色体短臂的连锁。侧翼标记为D7S1808和D7S1806，遗传距离为6.8 cM。多点连锁分析显示，标记D7S1808和D7S435之间的峰值多点LED值为6.89。连锁分析显示CMT轴突形态已被定位的1号和3号染色体标记的LED值为显著负值(值小于-2)，PFGE分析表明没有CMT1A重复，我们的发现与我们命名为CMT2D的一种新的轴索性CMT神经病的遗传类型一致。潜在的候选基因是多个T细胞伽马受体基因，它们映射到与CMT2D神经病相同的细胞遗传学区间。
Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe than of the feet with slow progressive course in 12 patients. Deep tendon reflexes were absent in the upper extremities and decreased in the lower extremities. There was distal hypesthesia for touch, proprioception and vibration sense for the hands more than for the feet. Motor nerve conduction velocities showed normal values (48-53 M/s) with normal latencies (2-3 msec) and electromyography revealed signs of denervation. Genetic linkage analysis used 167 short tandem repeat markers (STRPs) spaced throughout the 22 autosomes. Linkage to the short arm of chromosome 7 at 7p14 was found using the marker D7S435 (Z = 4.83 at theta = 0). Flanking markers were D7S1808 and D7S1806 and the genetic distance between them was 6.8 cM. The multipoint linkage analysis gave a peak multipoint led score of 6.89 between the markers D7S1808 and D7S435. Linkage analysis showed significantly negative led scores (with values less than -2) with markers of chromosomes 1 and 3 where CMT axonal forms have been previously mapped, PFGE analysis indicated the absence of the CMT1A duplication, Our findings are consistent with a new genetic type of axonal CMT neuropathy designated by us as CMT2D. Potential candidate genes are multiple T-cell gamma receptor genes which map to the same cytogenetic interval as CMT2D neuropathy.