Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta

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• 作者：M. Balasubramanian^a ; ^b ; ^{meena.balasubramanian@nhs.net} ; J. Hurst^c ; S. Brown^d ; N.J. Bishop^b ; ^e ; P. Arundel^b ; C. DeVile^b ; R.C. Pollitt^e ; ^f ; L. Crooks^f ; ^g ; D. Longman^h ; J.F. Caceres^h ; F. Shackleyⁱ ; S. Connolly^j ; J.H. Payne^k ; A.C. Offiah^b ; ^e ; D. Hughes^l ; DDD Study^m
• 关键词：Bone ; Fragility ; Osteogenesis imperfecta ; NBAS ; Nonsense mediated decay (NMD) ; Secretory pathway ; Collagen expression
• 刊名：Bone
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：94
• 期：Complete
• 页码：65-74
• 全文大小：2264 K
• 卷排序：94

文摘

Osteogenesis Imperfecta (OI) is the most commonest form of heritable bone fragility and predominantly a type 1 collagenopathy several autosomal recessive forms have also been described with a severe phenotype Here, we report two children with a severe bone fragility phenotype who underwent whole exome sequencing to establish their underlying genetic aetiology Compound heterozygous variants were identified in NBAS (Neuroblastoma amplified sequence gene). We report two patients with a bone fragility phenotype severe enough in childhood to require treatment with bisphosphonates with a positive response to treatment. We explore mechanism of action of NBAS and its role in bone fragility