Department of Pediatrics, University of California, San Diego, and Rady Children's Hospital, San Diego, California, USA.
The Scripps Translational Science Institute, La Jolla, California, USA.
Genet Med. 2017 Oct;19(10):1179-1183. doi: 10.1038/gim.2017.20. Epub 2017 Apr 6.
Nail-Patella syndrome is a dominantly inherited genetic disorder characterized by abnormalities of the nails, knees, elbows, and pelvis. Nail abnormalities are the most constant feature of Nail-Patella syndrome. Pathogenic mutations in a single gene, LMX1B, a mesenchymal determinant of dorsal-ventral patterning, explain approximately 95% of Nail-Patella syndrome cases. However, 5% of cases remain unexplained.
Here, we present exome sequencing and analysis of four generations of a family with a dominantly inherited Nail-Patella-like disorder (nail dysplasia with some features of Nail-Patella syndrome) who tested negative for LMX1B mutation.
We identify a loss-of-function mutation in WIF1 (NM_007191 p.W15*), which is involved in mesoderm segmentation, as the suspected cause of the Nail-Patella-like disorder observed in this family.
Mutation of WIF1 is a potential novel cause of a Nail-Patella-like disorder. Testing of additional patients negative for LMX1B mutation is needed to confirm this finding and further clarify the phenotype.Genet Med advance online publication 06 April 2017.
指甲髌骨综合征是一种常染色体显性遗传的基因疾病，其特征为指甲、膝盖、手肘和骨盆的异常。指甲异常是指甲髌骨综合征最常见的特征。约 95%的指甲髌骨综合征病例可由单个基因 LMX1B 的致病突变来解释，该基因为背腹模式形成的间质决定因素。然而，仍有 5%的病例原因不明。
我们对一个四代同堂的家族进行了外显子组测序和分析，该家族存在常染色体显性遗传的指甲髌骨样疾病（指甲发育不良伴指甲髌骨综合征的一些特征），但 LMX1B 突变检测结果为阴性。
我们发现 WIF1（NM_007191 p.W15*）中的一个功能丧失突变可能是导致该家族观察到的指甲髌骨样疾病的原因，WIF1 参与中胚层的节段形成。
WIF1 的突变可能是指甲髌骨样疾病的一个潜在新病因。需要对其他阴性的 LMX1B 突变患者进行检测以确认这一发现，并进一步阐明表型。遗传医学在线发表于 2017 年 4 月 6 日。
