Whittock Neil V, Turnpenny Peter D, Tuerlings Joep, Ellard Sian
Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK.
Prenat Diagn. 2003 Jul;23(7):575-9. doi: 10.1002/pd.643.
Autosomal recessive spondylocostal dysostosis type 1 (ARSCD1) is a member of the heterogeneous group of disorders termed the spondylocostal dysostoses that are characterized by multiple vertebral segmentation defects and rib anomalies. In these patients, the entire vertebral column is malformed and is replaced by multiple hemivertebrae giving rise to truncal shortening, abdominal protrusion and non-progressive spinal curvature. Genetic studies have shown that some cases of ARSCD are due to mutations in the somitogenesis gene, Delta-like 3 (DLL3), that encodes a ligand for the Notch signalling pathway-ARSCD type 1. To date, 17 different DLL3 gene mutations have been reported. A consanguineous family of Turkish origin with ARSCD type 1 due to a homozygous DLL3 mutation requested genetic prenatal diagnosis. Using DNA from a chorionic villus sample, both linkage analysis of the DLL3/19q region and direct sequencing for the familial mutation demonstrated that the unborn fetus was an unaffected carrier. This is the first case of molecular genetic prenatal diagnosis in any form of SCD.
常染色体隐性遗传性脊椎肋骨发育不良1型（ARSCD1）是脊椎肋骨发育不良这一异质性疾病组的成员，其特征为多个椎体节段性缺陷和肋骨异常。在这些患者中，整个脊柱畸形，被多个半椎体替代，导致躯干缩短、腹部突出和非进行性脊柱侧弯。遗传学研究表明，某些ARSCD病例是由于体节发生基因Delta样3（DLL3）突变所致，该基因编码Notch信号通路配体——1型ARSCD。迄今为止，已报道了17种不同的DLL3基因突变。一个因纯合DLL3突变而患1型ARSCD的土耳其近亲家庭要求进行基因产前诊断。利用绒毛膜绒毛样本的DNA，对DLL3/19q区域进行连锁分析并对家族性突变进行直接测序，结果表明未出生胎儿为未受影响的携带者。这是首例任何形式的脊柱肋骨发育不良的分子遗传学产前诊断病例。
