Axial spondylometaphyseal dysplasia is also caused by NEK1 mutations

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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.3107C>G (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.

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We thank the family for participating in the study. This study is supported by KAKENHI Grant-in-Aid for Scientific Research (B) (NMi, No 25293235), Takeda Science Foundation (ZW), and research grants from Japan Agency For Medical Research and Development (AMED) (SI, NMa, No 16ek0109068h0003). This study is also supported by the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet and by grants from Kronprinsessan Lovisas, Stiftelsen Frimurare Barnhuset in Stockholm, Hjärnfonden, Axel Tielmans Minnesfond, Samariten and Promobilia Foundations (GG, AN).

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Correspondence to Giedre Grigelioniene or Shiro Ikegawa.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on Journal of Human Genetics website

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