title: Axial spondylometaphyseal dysplasia is also caused by NEK1 mutations.
abstract: 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.
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.|Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet and Department of Pediatric Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Horemuzova
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
authors.forename: Long
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Clinical Neurophysiology, Karolinska University Hospital Huddinge and Department of Ophthalmology, The South Hospital, Stockholm, Sweden.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.affiliation: Department of Clinical Genetics and Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Clinical Genetics and Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Tham
authors.affiliation: Department of Clinical Genetics and Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Giedre
authors.initials: G
authors.lastname: Grigelioniene
authors.affiliation: Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D002648:Child; D003598:Cytoskeletal Proteins; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009154:Mutation; D000072380:NIMA-Related Kinase 1 / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics
chemical_list: C111475:CFAP410 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1