Vatanavicharn Nithiwat, Graham John M, Curry Cynthia J, Pepkowitz Samuel, Lachman Ralph S, Rimoin David L, Wilcox William R
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Am J Med Genet A. 2007 Oct 1;143A(19):2292-302. doi: 10.1002/ajmg.a.31934.
We report on six cases from four families with the newly described skeletal disorder diaphanospondylodysostosis (DSD). The characteristic radiographic findings included abnormal ossification of vertebral bodies, posterior rib gaps, missing ribs, and a downward tilt of the pubic rami, but normal long bones. The typical facial features of DSD cases were ocular hypertelorism, a short nose, depressed nasal bridge, and low set ears. Other distinctive findings included a short neck with bell-shaped thorax, and nephroblastomatosis. A history of consanguinity and affected siblings with unaffected parents supports autosomal recessive inheritance. Skeletal histology showed incomplete ossification of the ribs, vertebral bodies, and sacrum as well as incomplete formation of intervertebral discs. The posterior ribs were comprised of bone with intervening cartilage interrupted by dense fibrous tissue and skeletal muscle fascicles. These findings suggest abnormal development and differentiation of the paraxial mesoderm. Because of phenotypic similarities of DSD to Pax1 and Meox1 deficient mice, we sequenced genomic DNA from three unrelated DSD cases. No mutations were identified in the PAX1 and MEOX1 exons or flanking intronic sequences, excluding them as likely causative genes.
我们报告了来自四个家庭的六例患有新描述的骨骼疾病——透光性脊椎发育不全（DSD）的病例。特征性的影像学表现包括椎体骨化异常、后肋间隙、肋骨缺失以及耻骨支向下倾斜，但长骨正常。DSD病例的典型面部特征为眼距增宽、鼻子短、鼻梁凹陷和耳朵低位。其他独特表现包括短颈伴钟形胸廓以及肾母细胞瘤病。近亲结婚史以及父母未患病但有患病同胞支持常染色体隐性遗传。骨骼组织学显示肋骨、椎体和骶骨骨化不完全以及椎间盘形成不完全。后肋由骨组织构成，其间的软骨被致密纤维组织和骨骼肌束中断。这些发现提示轴旁中胚层发育和分化异常。由于DSD与Pax1和Meox1基因缺陷小鼠存在表型相似性，我们对三例无亲缘关系的DSD病例的基因组DNA进行了测序。在PAX1和MEOX1外显子或侧翼内含子序列中未发现突变，排除它们作为可能致病基因的可能性。
