Axial spondylometaphyseal dysplasia is also caused by NEK1 mutations
Axial spondylometaphyseal dysplasia is also caused by NEK1 mutations
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DOI：
10.1038/jhg.2016.157
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发表时间：
2017-04-01
影响因子：
3.5
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
--
作者：
Wang, Zheng;Horemuzova, Eva;Ikegawa, Shiro
轴向型腰椎间盘突出症（axial SMD）是一种以中轴骨骼发育不良和视网膜营养不良为特征的独特类型的SMD。最近，C21 orf 2已被确定为第一个轴向SMD的疾病基因;然而，已知存在遗传异质性。在这项研究中，我们确定NEK 1为轴向SMD的第二个致病基因。通过对轴型SMD患者进行全外显子组测序，我们鉴定了NEK 1，c.3107C4G（p.S1036*）和c.3830A>C（p.D1277A）的复合杂合突变，它们在家族中共分离。NEK 1突变先前已在三种类型的短肋胸营养不良中发现，这些短肋胸营养不良没有视网膜营养不良。我们的患者的骨骼表型比先前报道的NEK 1突变病例和轴向SMD携带C21 orf 2突变的病例要轻。与NEK 1突变相关的表型是可变的，骨骼纤毛病变中的表型-基因型相关性是具有挑战性的。
Axial spondylometaphyseal dysplasia (axial SMD) is a unique form of SMD characterized by dysplasia of axial skeleton and retinal dystrophy. Recently, C21orf2 has been identified as the first disease gene for axial SMD; however, the presence of genetic heterogeneity is known. In this study, we identified NEK1 as the second disease gene for axial SMD. By whole-exome sequencing in a patient with axial SMD, we identified compound heterozygous mutations of NEK1, c.3107C4G (p.S1036*) and c.3830A>C (p.D1277A), which co-segregated in the family. NEK1 mutations have previously been found in three types of short rib thoracic dystrophy, which have no retinal dystrophy. The skeletal phenotype of our patient was milder than those of previously reported cases with NEK1 mutations and those with axial SMD harboring C21orf2 mutations. Phenotypes associated with NEK1 mutations are variable and the phenotype-genotype corelation in skeletal ciliopathies is challenging.