PDF(Pubmed)
Abstract：
Malan syndrome is an autosomal dominant disorder caused by pathogenic variants in NFIX with less than 100 cases reported thus far. NFIX is important for stem cell proliferation, quiescence, and differentiation during development and its protein plays a role in replication, signal transduction, and transcription. As a result of pathogenic variants, symptoms of Malan syndrome include overgrowth, intellectual disability, speech delay, and dysmorphic features. Currently, the recurrence risk for this disorder is indicated at less than 1%, standard for de novo autosomal dominant disorders. Herein, we report an additional set of sisters with the same novel pathogenic variant in NFIX and clinical features consistent with Malan syndrome providing evidence of germline mosaicism. Considering the rarity of this condition in conjunction with three previous reports of germline mosaicism, it is worthwhile to investigate and re-evaluate the proper recurrence risk for this condition. This discovery would be paramount for family planning and genetic counseling practices in families with affected individuals.
摘要：
马兰综合征是NFIX中由致病性变异引起的常染色体显性疾病，迄今为止报告的病例少于100例。NFIX重要用于干细胞增殖，静止,在发育过程中分化，其蛋白质在复制中起作用，信号转导，和转录。由于致病变异，马兰综合征的症状包括过度生长，智力残疾,说话延迟,和畸形特征。目前,这种疾病的复发风险低于1%，从头常染色体显性疾病的标准。在这里，我们报告了另外一组在NFIX中具有相同新致病变异的姐妹,其临床特征与马兰综合征一致,提供了种系镶嵌性的证据.考虑到这种情况的罕见性，再加上以前的三份关于种系镶嵌的报告，值得研究和重新评估这种情况的适当复发风险.这一发现对于受影响个人家庭的计划生育和遗传咨询实践至关重要。
