Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase Ialpha, the alpha subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor beta2, and the diastrophic dysplasia sulfate-transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity.

中文翻译：

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通过连锁分析和纯合作图，将Netherton综合征基因定位于5q32染色体。

Netherton综合征（NS [MIM 256500]）是一种罕见且严重的常染色体隐性遗传疾病，其特征为先天性鱼鳞病，特定的毛干缺陷（无鞭毛）和特应性表现。患有这种综合征的婴儿通常不能fail壮成长。危及生命的并发症导致高产后死亡率。我们通过连锁分析和纯合性作图在NS的20个家庭中报告NS基因到染色体5q32的分配。获得了在标记D5S2017和D5S413之间连锁的重要证据（最大多点LOD得分10.11），没有证据表明基因座具有异质性。关键重组子的分析在小于3.5-cM的遗传区间内在标记D5S463和D5S2013之间绘制了NS基因座。NS基因座是5q31中细胞因子基因簇的端粒。编码酪蛋白激酶Ialpha，视网膜棒cGMP磷酸二酯酶的alpha亚基，有丝分裂纺锤体装配的调节剂，肾上腺素能受体beta2和非典型性硫酸盐异型增生转运蛋白基因的五个已知基因，以及映射在其中的38个表达序列标签关键区域，不是显而易见的候选人。我们的研究是向NS基因定位克隆的第一步。这一发现有望更好地了解控制表皮分化和免疫的分子机制。我们的研究是向NS基因定位克隆的第一步。这一发现有望更好地了解控制表皮分化和免疫的分子机制。我们的研究是向NS基因定位克隆的第一步。这一发现有望更好地了解控制表皮分化和免疫的分子机制。