Tysoe C, Saunders J, White L, Hills N, Nicol M, Evans G, Cole T, Chapman S, Pope F M
Connective Tissue Genetics Group, Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK.
QJM. 2003 Sep;96(9):663-71. doi: 10.1093/qjmed/hcg112.
Spondyloepimetaphyseal dysplasia (SEMD) is one of a clinically heterogeneous group of skeletal disorders, characterized by defective growth and modelling of the spine and long bones. Common clinical features include disproportionate short stature, malformed vertebrae and abnormal epiphyses or metaphyses. Some cases have been associated with mutations in the COL2A1 gene.
To determine whether the autosomal dominant Strudwick-type SEMD in a three-generation family, showing specific phenotypical features such as chest deformity, limb shortening, myopia and early-onset degenerative osteoarthrosis, might be caused by a novel COL2A1 mutation.
Genetic testing and clinical examination of family members.
Direct sequencing of PCR-amplified genomic DNA from the COL2A1 gene.
A point mutation within exon 20 of the COL2A1 gene was identified that substituted a glycine for an aspartic acid residue at codon 262.
All previously reported autosomal dominant mutations causing SEMD have substituted an obligate glycine within the triple helix, in particular at codons 292, 304 and 709 in the three reported Strudwick-type patients. Additionally, a recurrent glycine substitution at codon 154 has been identified in two unrelated Finnish cases with radiological features consistent with the Strudwick subtype. Our sixth helical glycine substitution extends the mutational spectrum and genotype/phenotype correlations of Strudwick-type SEMD.
脊椎骨骺发育不良（SEMD）是一组临床异质性骨骼疾病之一，其特征是脊柱和长骨生长及塑形缺陷。常见临床特征包括身材不成比例矮小、椎体畸形以及骨骺或干骺端异常。部分病例与COL2A1基因突变有关。
确定一个三代家族中呈现胸部畸形、肢体缩短、近视和早发性退行性骨关节炎等特定表型特征的常染色体显性Strudwick型SEMD是否可能由一种新的COL2A1突变引起。
对家族成员进行基因检测和临床检查。
对COL2A1基因经聚合酶链反应扩增的基因组DNA进行直接测序。
在COL2A1基因第20外显子内鉴定出一个点突变，该突变导致密码子262处的天冬氨酸残基被甘氨酸取代。
所有先前报道的导致SEMD的常染色体显性突变均在三螺旋内取代了一个特定的甘氨酸，特别是在三名报道的Strudwick型患者中的密码子292、304和709处。此外，在两例具有与Strudwick亚型一致的放射学特征的无关芬兰病例中，已鉴定出密码子154处反复出现的甘氨酸取代。我们的第六个螺旋甘氨酸取代扩展了Strudwick型SEMD的突变谱和基因型/表型相关性。
