Hentschel Julia, Tatun Dana, Parkhomchuk Dmitri, Kurth Ingo, Schimmel Bettina, Heinrich-Weltzien Roswitha, Bertzbach Sabine, Peters Hartmut, Beetz Christian
Institute of Human Genetics, Jena University Hospital, Jena, Germany; Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
Institute of Medical and Human Genetics, Charité, Universitaetsmedizin Berlin, Germany.
Gene. 2016 Sep 15;590(1):1-4. doi: 10.1016/j.gene.2016.05.040. Epub 2016 May 31.
Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous disorder of tooth development which is due to aberrant deposition or composition of enamel. Both syndromic and isolated forms exist; they may be inherited in an X-linked, autosomal recessive, or autosomal dominant manner. WDR72 is one of ten currently known genes for recessive isolated AI; nine WDR72 mutations affecting single nucleotides have been described to date. Based on whole exome sequencing in a large consanguineous AI pedigree, we obtained evidence for presence of a multi-exonic WDR72 deletion. A home-made multiplex ligation-dependent probe amplification assay was used to confirm the aberration, to narrow its extent, and to identify heterozygous carriers. Our study extends the mutational spectrum for WDR72 to include large deletions, and supports a relevance of the previously proposed loss-of-function mechanism. It also introduces an easy-to-use and highly sensitive tool for detecting WDR72 copy number alterations.
牙釉质发育不全（AI）是一种临床上和基因上均具有异质性的牙齿发育障碍，其原因是牙釉质的异常沉积或组成异常。它既有综合征型，也有非综合征型；可通过X连锁、常染色体隐性或常染色体显性方式遗传。WDR72是目前已知的十个隐性非综合征型AI相关基因之一；迄今为止，已描述了九个影响单核苷酸的WDR72突变。基于对一个大型近亲AI家系的全外显子组测序，我们获得了存在多外显子WDR72缺失的证据。使用自制的多重连接依赖探针扩增检测法来确认这种畸变，缩小其范围，并鉴定杂合携带者。我们的研究将WDR72的突变谱扩展到包括大片段缺失，并支持了之前提出的功能丧失机制的相关性。它还引入了一种易于使用且高度灵敏的工具来检测WDR72的拷贝数改变。
