Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian genetic isolates
Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian genetic isolates
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DOI：
10.1086/420795
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发表时间：
2004-05-01
影响因子：
9.8
通讯作者：
Samuels, ME
中科院分区：
文献类型：
--
作者：
Lafrenière, RG;MacDonald, MLE;Samuels, ME
遗传性感觉和自主神经病变（HSAN）II型是一种常染色体隐性遗传疾病，其特征是由于外周感觉神经元减少或缺失而导致的疼痛、温度和触觉受损。我们确定了两个大的谱系分离的疾病在一个孤立的人口生活在纽芬兰，并进行了5厘米的基因组扫描。连锁分析确定了一个位点定位到12p13.33，最大LOD得分为8.4。单倍型共享定义了一个1.06 Mb的候选区间，包含全部或部分7个注释基因，测序未能检测到致病突变。比较基因组学揭示了一个保守的ORF对应一个新的基因，其中我们发现了三个不同的截断突变的五个家庭，包括农村魁北克和新斯科舍省的患者。该基因称为“HSN 2”，由位于PRKWNK 1基因内含子8内的单个外显子组成，并从同一条链转录。HSN 2蛋白可能在外周感觉神经元或其支持的雪旺细胞的发育和/或维持中起作用。
Hereditary sensory and autonomic neuropathy ( HSAN) type II is an autosomal recessive disorder characterized by impairment of pain, temperature, and touch sensation owing to reduction or absence of peripheral sensory neurons. We identified two large pedigrees segregating the disorder in an isolated population living in Newfoundland and performed a 5-cM genome scan. Linkage analysis identified a locus mapping to 12p13.33 with a maximum LOD score of 8.4. Haplotype sharing defined a candidate interval of 1.06 Mb containing all or part of seven annotated genes, sequencing of which failed to detect causative mutations. Comparative genomics revealed a conserved ORF corresponding to a novel gene in which we found three different truncating mutations among five families including patients from rural Quebec and Nova Scotia. This gene, termed "HSN2," consists of a single exon located within intron 8 of the PRKWNK1 gene and is transcribed from the same strand. The HSN2 protein may play a role in the development and/or maintenance of peripheral sensory neurons or their supporting Schwann cells.