Lehmann O J, Ebenezer N D, Jordan T, Fox M, Ocaka L, Payne A, Leroy B P, Clark B J, Hitchings R A, Povey S, Khaw P T, Bhattacharya S S
Department of Molecular Genetics, Institute of Ophthalmology, London, England EC1V 9EL.
Am J Hum Genet. 2000 Nov;67(5):1129-35. doi: 10.1016/S0002-9297(07)62943-7. Epub 2000 Sep 27.
The forkhead transcription factor gene FOXC1 (formerly FKHL7) is responsible for a number of glaucoma phenotypes in families in which the disease maps to 6p25, although mutations have not been found in all families in which the disease maps to this region. In a large pedigree with iris hypoplasia and glaucoma mapping to 6p25 (peak LOD score 6.20 [recombination fraction 0] at D6S967), no FOXC1 mutations were detected by direct sequencing. However, genotyping with microsatellite repeat markers suggested the presence of a chromosomal duplication that segregated with the disease phenotype. The duplication was confirmed in affected individuals by FISH with markers encompassing FOXC1. These results provide evidence of gene duplication causing developmental disease in humans, with increased gene dosage of either FOXC1 or other, as yet unknown genes within the duplicated segment being the probable mechanism responsible for the phenotype.
叉头转录因子基因FOXC1（原名FKHL7）与一些青光眼表型相关，在某些家系中，该疾病定位于6p25，尽管并非所有定位于该区域的家系中都发现了突变。在一个患有虹膜发育不全和青光眼且定位于6p25的大家系中（在D6S967处的最高对数优势分数为6.20[重组率为0]），通过直接测序未检测到FOXC1突变。然而，使用微卫星重复标记进行基因分型提示存在一个与疾病表型共分离的染色体重复。通过使用包含FOXC1的标记进行荧光原位杂交（FISH），在受影响个体中证实了该重复。这些结果提供了基因重复导致人类发育性疾病的证据，重复片段内FOXC1或其他尚未明确的基因的基因剂量增加可能是导致该表型的机制。
