X-linked spondyloepiphyseal dysplasia tarda: Novel and recurrent mutations in 13 European families.
X-linked spondyloepiphyseal dysplasia tarda: Novel and recurrent mutations in 13 European families.
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DOI：
10.1002/humu.9254
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发表时间：
2004-07-01
期刊：
影响因子：
3.9
通讯作者：
Brenner, Rolf E
中科院分区：
文献类型：
--
作者：
Fiedler, Jorg;Le Merrer, Martine;Brenner, Rolf E
X连锁迟发性脊柱骨骺发育不良是一种骨性发育不良，主要累及椎体和骨骺，常与退行性关节疾病的早期发展有关。放射学上，该病的特点是椎体呈典型的驼峰状畸形。SEDT是由位于Xp22.12-p22.31上的SEDL突变引起的。为了进一步阐明潜在的变异谱，我们对13个欧洲SEDT家系的所有6个SEDL外显子进行了筛选，并鉴定了6个新的(c.99delC，c.183_184delGA，c.236-5_236-8delATTA，c.325delT，c.345_346delTG，c.94-？423+？DEL)和9个以前报道的突变(c.1-？93+？DEL，c.93+5G>；A，c.157_158delAT，c.210G>；C.236-9_236-12delTTAA，c.267_275delAAGAC，c.324-4_324-10delTCTTTCCinsAA)。在3个无亲缘关系的家系中发现了反复发生的剪接位点突变C.93+5G>；A(以前描述为IVS3+5G>；A)。两名患者携带2个等位基因的变化。在一个病例中，外显子4的一个新的变异(c.99delC)与内含子4中的几个核苷酸缺失(c.236-5_236-8delATTA)有关，在第二个病例中，我们发现了一个先前报道的转变c.210G>；A和一个新的外显子6的缺失(c.325delT)。所有已鉴定的序列变异要么是完整外显子的缺失，要么是预测导致过早终止密码子或导致剪接缺陷，并与相当一部分sedlin蛋白的丢失有关。
X-linked spondyloepiphyseal dysplasia tarda is a skeletal dysplasia mainly affecting the vertebrae and epiphyses and commonly associated with the early development of degenerative joint disease. Radiographically the disorder is characterized by a typical hump-shaped deformity of the vertebral bodies. SEDT is caused by mutations in SEDL located on Xp22.12-p22.31. To further elucidate the spectrum of underlying variations we performed a screening of all 6 exons of SEDL within 13 European SEDT families and identified 6 new (c.99delC, c.183_184delGA, c.236-5_236-8delATTA, c.325delT, c.345_346delTG, c.94-?_423+?del) and 9 previously reported mutations (c.1-?_93+?del, c.93+5G>A, c.157_158delAT, c.210G>A, c.236-9_236-12delTTAA, c.267_275delAAGAC, c.324-4_324-10delTCTTTCCinsAA). The recurrent splice site alteration c.93+5G>A (formerly described as IVS3+5G>A) was detected in 3 unrelated families. Two patients were carrying 2 changes in the allele. In one case, a novel variation in exon 4 (c.99delC) was associated with several nucleotide deletions in intron 4 (c.236-5_236-8delATTA), and in the second case we identified a previously reported transition c.210G>A and a novel deletion in exon 6 (c.325delT). All sequence variations identified are either deletions of complete exons or predicted to result in a premature stop codon or to lead into splicing defects and are associated with a loss of considerable parts of the sedlin protein.