Wijmenga C, van den Heuvel L P, Strengman E, Luyten J A, van der Burgt I J, de Groot R, Smeets D F, Draaisma J M, van Dongen J J, De Abreu R A, Pearson P L, Sandkuijl L A, Weemaes C M
Department of Human Genetics, Utrecht University, Utrecht, The Netherlands.
Am J Hum Genet. 1998 Sep;63(3):803-9. doi: 10.1086/302021.
Immunodeficiency in association with centromere instability of chromosomes 1, 9, and 16 and facial anomalies (ICF syndrome) is a rare autosomal recessive disorder. ICF patients show marked hypomethylation of their DNA; undermethylation of classical satellites II and III is thought to be associated with the centromere instability. We used DNA from three consanguineous families with a total of four ICF patients and performed a total genome screen, to localize the ICF syndrome gene by homozygosity mapping. One chromosomal region (20q11-q13) was consistently found to be homozygous in ICF patients, whereas all healthy sibs showed a heterozygous pattern. Comparison of the regions of homozygosity in the four ICF patients localized the ICF locus to a 9-cM region between the markers D20S477 and D20S850. Analysis of more families will be required, to refine the map location further. Isolation of the gene associated with the ICF syndrome not only will give insight into the etiology of the ICF syndrome but will also broaden our understanding of DNA methylation processes.
免疫缺陷伴1、9和16号染色体着丝粒不稳定及面部异常（ICF综合征）是一种罕见的常染色体隐性疾病。ICF患者的DNA表现出明显的低甲基化；经典卫星序列II和III的低甲基化被认为与着丝粒不稳定有关。我们使用了来自三个近亲家庭共四名ICF患者的DNA进行全基因组筛查，通过纯合性定位来确定ICF综合征基因的位置。在ICF患者中始终发现一个染色体区域（20q11 - q13）是纯合的，而所有健康的同胞均表现为杂合模式。对四名ICF患者的纯合区域进行比较，将ICF基因座定位在标记D20S477和D20S850之间9厘摩的区域。需要分析更多的家庭以进一步精确该图谱位置。分离与ICF综合征相关的基因不仅将深入了解ICF综合征的病因，还将拓宽我们对DNA甲基化过程的理解。
