Toutain A, Ronce N, Dessay B, Robb L, Francannet C, Le Merrer M, Briard M L, Kaplan J, Moraine C
Service de Génétique, Hôpital Bretonneau, Centre Hospitalo-Universitaire, Tours, France.
Hum Genet. 1997 Feb;99(2):256-61. doi: 10.1007/s004390050349.
Nance-Horan syndrome (NHS) is an X-linked disease characterized by severe congenital cataract with microcornea, distinctive dental findings, evocative facial features and mental impairment in some cases. Previous linkage studies have placed the NHS gene in a large region from DXS143 (Xp22.31) to DXS451 (Xp22.13). To refine this localization further, we have performed linkage analysis in four families. As the maximum expected Lod score is reached in each family for several markers in the Xp22.31-p22.13 region and linkage to the rest of the X chromosome can be excluded, our study shows that NHS is a genetically homogeneous condition. An overall maximum two-point Lod score of 9.36 (theta = 0.00) is obtained with two closely linked markers taken together. DXS207 and DXS1053 in Xp22.2. Recombinant haplotypes indicate that the NHS gene lies between DXS85 and DXS1226. Multipoint analysis yield a maximum Lod score of 9.45 with the support interval spanning a 15-cM region that includes DXS16 and DXS1229/365. The deletion map of the Xp22.3-Xp21.3 region suggests that the phenotypic variability of NHS is not related to gross rearrangement of sequences of varying size but rather to allelic mutations in a single gene, presumably located proximal to DXS16 and distal to DXS1226. Comparison with the map position of the mouse Xcat mutation supports the location of the NHS gene between the GRPR and PDHA1 genes in Xp22.2.
南斯-霍兰综合征（NHS）是一种X连锁疾病，其特征为严重先天性白内障合并小角膜、独特的牙齿表现、引人注目的面部特征，部分病例伴有智力障碍。先前的连锁研究已将NHS基因定位在从DXS143（Xp22.31）至DXS451（Xp22.13）的大片区域。为进一步精确该定位，我们对四个家系进行了连锁分析。由于Xp22.31 - p22.13区域的多个标记在每个家系中均达到最大期望Lod分值，且可排除与X染色体其余部分的连锁关系，我们的研究表明NHS是一种基因同质疾病。两个紧密连锁的标记DXS207和位于Xp22.2的DXS1053共同获得的总体最大两点Lod分值为9.36（θ = 0.00）。重组单倍型表明NHS基因位于DXS85和DXS1226之间。多点分析获得的最大Lod分值为9.45，支持区间跨越一个15厘摩的区域，该区域包括DXS16和DXS1229/365。Xp22.3 - Xp21.3区域的缺失图谱表明，NHS的表型变异性并非与不同大小序列的大规模重排相关，而是与单个基因中的等位基因突变有关，该基因可能位于DXS16近端和DXS1226远端。与小鼠Xcat突变的图谱位置比较支持NHS基因位于Xp22.2的GRPR和PDHA1基因之间。
