Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25
Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25
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DOI：
10.1038/sj.ejhg.5200354
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发表时间：
2000-01-01
影响因子：
5.2
通讯作者：
Walter, MA
中科院分区：
文献类型：
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作者：
Mirzayans, F;Gould, DB;Walter, MA
叉头样7（FKHL 7）基因的突变最近已被证明会导致青少年青光眼和眼前节异常。我们报告了一个三代家族的Axenovirus-Rieger综合征（ARS），窝藏在FKHL 7基因的改变。遗传连锁分析排除ARS表型从染色体4 q25和13 q14，PITX 2和RIEG 2基因座的位置，分别。在6p 25的标记处观察到连锁的证据，靠近FKHL 7基因。FKHL 7的直接测序检测到C67 T突变，该突变在该家族中与ARS表型分离，但在超过80条对照染色体中未检测到。预测该突变引起叉头DNA结合结构域上游的FKHL 7蛋白（Gln 23 Stop）的无义突变，从而产生截短的FKHL 7蛋白产物。这一发现广泛地暗示了FKHL 7在眼、颅面、牙齿和脐带发育中的作用。
Mutations in the forkhead-like 7 (FKHL7) gene have been recently shown to cause juvenile glaucoma and anterior segment anomalies. We report on a three-generation family with Axenfeld-Rieger syndrome (ARS), harboring an alteration in the FKHL7 gene. Genetic linkage analyses excluded the ARS phenotype from chromosomes 4q25 and 13q14, the locations of the PITX2 and RIEG2 loci, respectively. Evidence of linkage was observed with markers at 6p25, near the FKHL7 gene. Direct sequencing of FKHL7 detected a C67T mutation that segregated with the ARS phenotype in this family, but was not detected in over 80 control chromosomes. This mutation is predicted to cause a nonsense mutation of the FKHL7 protein (Gln23Stop) upstream of the forkhead DNA-binding domain, and thus to generate a truncated FKHL7 protein product. This discovery broadly implicates FKHL7 in ocular, craniofacial, dental, and umbilical development.