Purchase this article with an account.
Anne H. Child, Jose A. Aragon-Martin, Kathryn B. Hughes, Roshanak Sharafieh, David Charteris, Gavin Arno; Genetic Screening Of Ectopia Lentis Patients For Mutations In ADAMTSL4, ADAMTS17 and LTBP2. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3932.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Ectopia Lentis (EL) is clinically and genetically heterogeneous (autosomal dominant - MIM 129600; autosomal recessive - MIM 225100). The dominant form can arise through mutations in FBN1, at the milder end of the type-1 fibrillinopathy spectrum. The recessive form has been associated with ADAMTSL4 mutations, and later with ADAMTS17 in incomplete Weill-Marchesani syndrome featuring EL. Recently, it has been linked to LTBP2 (null mutations in two unrelated families with microspherophakia and progressive EL).
Of 42 probands with EL that were screened for FBN1 mutations, 23 had mutations in FBN1. Nineteen were screened for mutations in all exons including intron/exon boundaries of ADAMTSL4, ADAMTS17 and LTBP2 genes. These 19 probands did not fulfil the Ghent criteria for Marfan syndrome and demonstrated no heart involvement on echocardiogram.
In 8/19, mutations in ADAMTSL4 were found. There were no mutations found in ADAMTS17 and LTBP2. Two intronic variations were found in ADAMTS17 but splice site prediction excluded them.
This study supports the evidence that homozygous and compound heterozygous mutations in ADAMTSL4 are associated with autosomal recessive EL. A larger series of probands needs to be studied to determine whether ADAMTS17 and LTBP2 are causative genes in EL, and to identify further causative genes. In our UK patients with EL, LTBP2 mutations have not been demonstrated, suggesting ethnic or syndromic associations in the initial reports in Turkish and Pakistani families. The identification of a causative mutation in ADAMTSL4 will exclude Marfan syndrome in EL patients and guide clinical management, of particular relevance in young children affected with EL. In our population we screen first for FBN1 mutations in marfanoid patients with dominant pedigrees, and first for ADAMTSL4 in apparently autosomal recessive pedigrees.
This PDF is available to Subscribers Only