Temtamy Samia A, Aglan Mona S, Valencia Maria, Cocchi Guido, Pacheco Maria, Ashour Adel M, Amr Khalda S, Helmy Sanaa M H, El-Gammal Mona A, Wright Michael, Lapunzina Pablo, Goodship Judith A, Ruiz-Perez Victor L
Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Hum Mutat. 2008 Jul;29(7):931-8. doi: 10.1002/humu.20778.
Previous work has shown Ellis-van Creveld (EvC) patients with mutations either in both alleles of EVC or in both alleles of EVC2. We now report affected individuals with the two genes inactivated on each allele. In a consanguineous pedigree diagnosed with EvC and borderline intelligence, we detected a 520-kb homozygous deletion comprising EVC, EVC2, C4orf6, and STK32B, caused by recombination between long interspersed nuclear element-1 (LINE-1 or L1) elements. Patients homozygous for the deletion are deficient in EVC and EVC2 and have no increase in the severity of the EvC typical features. Similarly deletion carriers demonstrate absence of digenic inheritance in EvC. Further, the phenotype of these patients suggests that the EVC-STK32B deletion also leads to mild mental retardation and reveals that loss of the novel genes C4orf6 and STK32B causes at most mild mental deficit. In an EvC compound heterozygote of different ethnic origin we identified the same LINE-to-LINE rearrangement due to a different recombination event. These findings highlight the importance of L1 repetitive sequences in human genome architecture and disease.
先前的研究表明，患有埃利斯-范克里弗德综合征（EvC）的患者，其EVC两个等位基因或EVC2两个等位基因均发生了突变。我们现在报告了每个等位基因上这两个基因均失活的受影响个体。在一个被诊断为EvC且伴有边缘智力的近亲家系中，我们检测到一个520 kb的纯合缺失，该缺失包含EVC、EVC2、C4orf6和STK32B，是由长散在核元件1（LINE-1或L1）元件之间的重组引起的。该缺失的纯合患者缺乏EVC和EVC2，EvC典型特征的严重程度也没有增加。同样，缺失携带者在EvC中也未表现出双基因遗传。此外，这些患者的表型表明，EVC-STK32B缺失也会导致轻度智力发育迟缓，并揭示新基因C4orf6和STK32B的缺失最多只会导致轻度智力缺陷。在一个不同种族来源的EvC复合杂合子中，我们由于不同的重组事件鉴定出了相同的LINE-to-LINE重排。这些发现突出了L1重复序列在人类基因组结构和疾病中的重要性。
