Nicholson G A, Dawkins J L, Blair I P, Kennerson M L, Gordon M J, Cherryson A K, Nash J, Bananis T
Molecular Medicine Laboratory, University of Sydney, NSW, Australia.
Nat Genet. 1996 May;13(1):101-4. doi: 10.1038/ng0596-101.
Hereditary sensory neuropathy type I (HSN-I, also known as hereditary sensory and autonomic neuropathy type I (HSAN-I), or hereditary sensory radicular neuropathy) is an autosomal dominant disorder that is the most common of a group of degenerative disorders of sensory neurons. HSN-I was initially recognized as a disease that produced mutilating ulceration leading to amputation of digits (Fig. 1). It was given names such as familial ulcers with mutilating lesions of the extremities and perforating ulcers with osseous atrophy. The disease involves a progressive degeneration of dorsal root ganglion and motor neurons, leading to distal sensory loss and later distal muscle wasting and weakness and variable neural deafness. Sensory deficits include loss of all modalities, particularly loss of sensation to pain and temperature. Skin injuries may lead to chronic skin ulcers, osteomyelitis, and extrusion of bone fragments, especially the metatarsals. Onset of symptoms is in the second or later decades. We undertook a genome screen using linkage analysis in four Australian HSN-I kindreds. We now show that the HSN1 gene maps to an 8-centiMorgan (cM) region flanked by D9S318 and D9S176 on chromosome 9q22.1-q22.3. Multipoint linkage analysis suggests a most likely location at D9S287, within a 4.9-cM confidence interval.
遗传性感觉神经病I型（HSN-I，也称为遗传性感觉和自主神经病I型（HSAN-I），或遗传性感觉神经根神经病）是一种常染色体显性疾病，是感觉神经元一组退行性疾病中最常见的一种。HSN-I最初被认为是一种导致致残性溃疡并最终导致手指截肢的疾病（图1）。它曾被赋予诸如伴有肢体致残性病变的家族性溃疡和伴有骨质萎缩的穿孔性溃疡等名称。该疾病涉及背根神经节和运动神经元的进行性退化，导致远端感觉丧失，随后出现远端肌肉萎缩、无力以及不同程度的神经性耳聋。感觉缺陷包括所有感觉方式的丧失，尤其是痛觉和温度觉丧失。皮肤损伤可能导致慢性皮肤溃疡、骨髓炎以及骨碎片（尤其是跖骨）外露。症状通常在第二个十年或更晚开始出现。我们利用连锁分析对四个澳大利亚HSN-I家系进行了基因组筛查。我们现在表明，HSN1基因定位于9号染色体9q22.1-q22.3上，位于D9S318和D9S176之间的一个8厘摩（cM）区域。多点连锁分析表明最可能的位置在D9S287，位于一个4.9厘摩的置信区间内。
