Ramírez-Castro J L, Pineda-Trujillo N, Valencia A V, Muñetón C M, Botero O, Trujillo O, Vásquez G, Mora B E, Durango N, Bedoya G, Ruiz-Linares A
Unidad de Genética Medica, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Am J Med Genet. 2002 Nov 15;113(1):47-51. doi: 10.1002/ajmg.10741.
We report the genetic characterization of one family with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type 1 and two families with BPES type 2 from a historically isolated population in northwest Colombia. Linkage and haplotype analyses indicate that BPES in these families is linked to 3q23. Mutation screening of FOXL2 in the family with BPES type 1 revealed a novel 394C --> T nonsense mutation which deletes the forkhead DNA binding domain. The two families with BPES type 2 both carry an in-frame 30 bp duplication that leads to the elongation of a polyalanine tract. This duplication has been previously reported in Europe, where recurrent mutation has been demonstrated in unrelated familial and sporadic BPES cases. The recurrent nature of this duplication seems to relate to the secondary structure of this DNA region. The genotype-phenotype correlation seen in the Colombian families is consistent with the recent proposal that BPES type 1 is caused by truncating mutations leading to haploinsufficiency, while BPES type 2 is due to mutations generating elongated protein products.
我们报告了来自哥伦比亚西北部一个历史上孤立的人群中的一个1型睑裂狭小-上睑下垂-内眦赘皮综合征（BPES）家族和两个2型BPES家族的基因特征。连锁和单倍型分析表明，这些家族中的BPES与3q23连锁。对1型BPES家族的FOXL2进行突变筛查，发现了一个新的394C→T无义突变，该突变删除了叉头DNA结合域。两个2型BPES家族均携带一个框内30 bp重复，导致多聚丙氨酸序列延长。这种重复先前在欧洲已有报道，在无关的家族性和散发性BPES病例中已证实存在复发性突变。这种重复的复发性似乎与该DNA区域的二级结构有关。在哥伦比亚家族中观察到的基因型-表型相关性与最近的提议一致，即1型BPES由导致单倍体不足的截短突变引起，而2型BPES则归因于产生延长蛋白产物的突变。
