Axial Spondylometaphyseal Dysplasia Is Caused by C21orf2 Mutations.

Autor: Wang Z; Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.; McKusick-Zhang Center for Genetic Medicine and State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China., Iida A; Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan., Miyake N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan., Nishiguchi KM; Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan., Fujita K; Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan., Nakazawa T; Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan.; Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan.; Department of Opthalmology, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan., Alswaid A; Department of Pediatrics, King Abdulaziz Medical City for National Guard Health Affairs, Riyadh, 22490, Saudi Arabia., Albalwi MA; Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, 22490, Saudi Arabia., Kim OH; Department of Radiology, Woorisoa Children's Hospital, Seoul, 08291, Republic of Korea., Cho TJ; Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea., Lim GY; Department of Radiology, St. Mary's Hospital, The Catholic University, Seoul, 07345, Republic of Korea., Isidor B; CHU Nantes, Service de Génétique Médicale and INSERM, UMR-S 957, Nantes, 44093, France., David A; CHU Nantes, Service de Génétique Médicale and INSERM, UMR-S 957, Nantes, 44093, France., Rustad CF; Department of Medical Genetics, Section for Clinical Genetics, Oslo University Hospital, Oslo, 0424, Norway., Merckoll E; Department of Radiology, Oslo University Hospital, Oslo, 0424, Norway., Westvik J; Department of Radiology, Oslo University Hospital, Oslo, 0424, Norway., Stattin EL; Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, 90187, Sweden., Grigelioniene G; Department of Clinical Genetics and Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, 17176, Sweden., Kou I; Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan., Nakajima M; Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan., Ohashi H; Division of Medical Genetics, Saitama Children's Medical Center, Saitama, 339-8551, Japan., Smithson S; Department of Clinical Genetics, St. Michaels Hospital, Bristol, BS2 8EG, United Kingdom., Matsumoto N; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan., Nishimura G; Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Fuchu, 183-8561, Japan., Ikegawa S; Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2016 Mar 14; Vol. 11 (3), pp. e0150555. Date of Electronic Publication: 2016 Mar 14 (Print Publication: 2016).
DOI: 10.1371/journal.pone.0150555
Abstrakt: Axial spondylometaphyseal dysplasia (axial SMD) is an autosomal recessive disease characterized by dysplasia of axial skeleton and retinal dystrophy. We conducted whole exome sequencing and identified C21orf2 (chromosome 21 open reading frame 2) as a disease gene for axial SMD. C21orf2 mutations have been recently found to cause isolated retinal degeneration and Jeune syndrome. We found a total of five biallelic C21orf2 mutations in six families out of nine: three missense and two splicing mutations in patients with various ethnic backgrounds. The pathogenic effects of the splicing (splice-site and branch-point) mutations were confirmed on RNA level, which showed complex patterns of abnormal splicing. C21orf2 mutations presented with a wide range of skeletal phenotypes, including cupped and flared anterior ends of ribs, lacy ilia and metaphyseal dysplasia of proximal femora. Analysis of patients without C21orf2 mutation indicated genetic heterogeneity of axial SMD. Functional data in chondrocyte suggest C21orf2 is implicated in cartilage differentiation. C21orf2 protein was localized to the connecting cilium of the cone and rod photoreceptors, confirming its significance in retinal function. Our study indicates that axial SMD is a member of a unique group of ciliopathy affecting skeleton and retina.
Databáze: MEDLINE
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