Ells Anna, Guernsey Duane L, Wallace Karin, Zheng Binyou, Vincer Michael, Allen Alexander, Ingram April, DaSilva Orlando, Siebert Lee, Sheidow Thomas, Beis Jill, Robitaille Johane M
Calgary Retina Consultants, Calgary, Alberta, Canada.
Ophthalmic Genet. 2010 Mar;31(1):37-43. doi: 10.3109/13816810903479834.
To determine whether mutations in the FZD4 gene are a risk factor for developing severe ROP.
Three Canadian tertiary care centers recruited premature infants prospectively and retrospectively, and assigned affectation status based on the maximum degree of severity of ROP recorded in both eyes. Mutation screening of the FZD4 gene was performed using direct sequencing. All sequence changes were evaluated for functional significance.
Two novel FZD4 mutations (Ala370Gly or Lys203Asn) were identified in two infants from the severe ROP group (n=71). No mutation was detected in the mild to no ROP group (n=33), and the two novel mutations were absent in 173 random Caucasian samples. Mutation Ala370Gly was also found in one sibling and one parent of the affected infant, but no signs of familial exudative vitreoretinopathy (FEVR), a condition with phenotypic overlap with ROP known to be caused by FZD4 mutations, were present in either family member.
Mutations in the FZD4 gene in this group of premature infants supports a role for the FZD4 pathway in the development of severe ROP and accounts for approximately 3% of severe ROP in Caucasian premature infants.
确定FZD4基因的突变是否是发生严重视网膜病变（ROP）的危险因素。
三个加拿大三级护理中心前瞻性和回顾性地招募早产儿，并根据双眼记录的ROP严重程度的最大程度确定患病状态。使用直接测序法对FZD4基因进行突变筛查。对所有序列变化进行功能意义评估。
在严重ROP组的两名婴儿（n = 71）中鉴定出两个新的FZD4突变（Ala370Gly或Lys203Asn）。在轻度至无ROP组（n = 33）中未检测到突变，并且在173个随机白种人样本中不存在这两个新突变。在受影响婴儿的一名兄弟姐妹和一名父母中也发现了Ala370Gly突变，但两名家庭成员均未出现家族性渗出性玻璃体视网膜病变（FEVR）的迹象，FEVR是一种与已知由FZD4突变引起的ROP有表型重叠的疾病。
这组早产儿中FZD4基因的突变支持FZD4通路在严重ROP发生中的作用，并且在白种人早产儿严重ROP中约占3%。
