Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I
Germinal mosaicism of PAX3 mutation caused Waardenburg syndrome type I
复制标题
PAX3突变的胚芽嵌合导致I型瓦登堡综合征。
DOI：
10.1016/j.ijporl.2017.11.011
复制
发表时间：
2018-01-01
影响因子：
1.5
通讯作者：
Jiang, Hongyan
中科院分区：
文献类型：
--
作者：
Chen, Kaitian;Zhan, Yuan;Jiang, Hongyan
目的：Waardenburg综合征突变最常复发或新发。家庭复发率低，有几个受影响的孩子的家庭非常罕见。在这项研究中，我们的目的是澄清潜在的遗传原因Waardenburg综合征I型在两个兄弟姐妹在一个中国家庭中，母亲受语前轻度听力损失和父亲谁是阴性的Waardenburg综合征的临床症状，并有正常的听力阈值。方法：记录了家庭成员的完整特征，并进行了基因测序和父母-结果：发现两个先证者在PAX 3/GJB 2基因上有共同的双突变，导致Waardenburg综合征I型并发听力损失。他们的母亲携带GJB 2 c.109G > A纯合突变;然而，既没有新的PAX 3 c.592deIG突变，也没有Waardenburg综合征的表型，观察在任何parent.Conclusion：这些以前未报道的PAX 3/GJB 2的双基因突变导致耳聋与Waardenburg综合征I型在这个家庭。据我们所知，这是第一个报告描述Germinal镶嵌在Waardenburg综合征。这个概念很重要，因为它使这个家庭关于在随后的怀孕中突变复发风险的遗传咨询复杂化。
Objectives: Waardenburg syndrome mutations are most often recurrent or de novo. The rate of familial recurrence is low and families with several affected children are extremely rare. In this study, we aimed to clarify the underlying hereditary cause of Waardenburg syndrome type I in two siblings in a Chinese family, with a mother affected by prelingual mild hearing loss and a father who was negative for clinical symptoms of Waardenburg syndrome and had a normal hearing threshold.Methods: Complete characteristic features of the family members were recorded and genetic sequencing and parent-child relationship analyses were performed.Results: The two probands were found to share double mutations in the PAX3/GJB2 genes that caused concurrent hearing loss in Waardenburg syndrome type I. Their mother carried the GJB2 c.109G > A homozygous mutation; however, neither the novel PAX3 c.592deIG mutation, nor the Waardenburg syndrome phenotype, was observed in either parent.Conclusion: These previously unreported digenic mutations in PAX3/GJB2 resulted in deafness associated with Waardenburg syndrome type I in this family. To our knowledge, this is the first report describing germinal mosaicism in Waardenburg syndrome. This concept is important because it complicates genetic counseling of this family regarding the risk of recurrence of the mutations in subsequent pregnancies.