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| New Compound Heterozygous Mutations detected in the ADAMTSL4 Cause Autosomal-Recessive Isolated Bilateral Ectopia Lentis |
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| 作者：余文瀚 文章来源：Ophthalmic Laboratories & Department of Ophthalmology, West China Hospital, Sichuan University, 610041 点击数175 更新时间：2012/9/13 文章录入：毛进 责任编辑：毛进 |
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Purpose To analyze the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) like-4 gene in a Chinese pedigree with Ectopia lentis (EL).
Methods In this two-generation family, four members out of seven of the 2nd generation were affected while those of 1st generation were normal. Complete ophthalmologic examinations of all members were conducted. The coding regions and flanking sequences of human ADAMTSL4 gene were amplified by polymerase chain reaction (PCR), sequenced and compared with reference database. Co-Immunoprecipitation was conducted to identify the interaction between wide type (WT) / mutant (MT) ADAMTSL4 and Fibrillin-1 in protein level.
Results New compound heterozygote mutations in the ADAMTSL4 gene were identified in this family. An insertion mutation (c.1784insT) in exon 11 and a missense mutation (c.594 G>A, p.R865H) in exon 16, both of which were respectively inherited from the patient’s unaffected parents, contributed to this disease. Both mutation sites were conserved in evolution. The mutant ADAMTSL4 failed to interact with Fibrillin-1 protein while wide type protein was shown to derectly bind to Fibrillin-1.
Conclusions A new compound heterozygote mutations of ADAMTSL4 was identified in this IEL family, indicating ADAMTSL4 may play an important role in the development and/or integrity of the zonular fibers by contributing to the assembly of Fibrillin fibres. |
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