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A. H. Child, J. A. Aragon-Martin, D. Ahnood, D. Charteris, A. Saggar, G. Arno; Role of ADAMTSL4 Mutations in FBN1 Mutation Negative Ectopia Lentis Patients. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4770.
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Although clinically homogeneous, ectopia lentis (EL) is genetically heterogeneous with both autosomal-dominant (MIM 129600) and autosomal-recessive (MIM 225100) forms. The dominant disorder can be caused by mutations in FBN1, at the milder end of the type-1 fibrillinopathy spectrum. Recently in a consanguineous Jordanian family, recessive EL was mapped to locus 1q21 containing the ADAMTSL4 gene and a nonsense mutation found in exon 11 (c.1785T>G, p.Y595X) of ADAMTSL4.
In this study, 12 consecutive Caucasian U.K. probands with EL and demonstrating no, or very mild, heart involvement on echocardiogram were included. Probands did not fulfil the Ghent criteria for Marfan syndrome and were previously found mutation-negative for FBN1. Mutation screening in ADAMTSL4 by direct sequencing of all exons including their intron/exon boundaries was performed.
Homozygous or compound heterozygous mutations were identified in 6/12 (50%) probands. Mutation data are summarised in table 1. Where available, familial screening of these families confirmed the mutation co-segregated with the EL phenotype. None of the ADAMTSL4 mutations described here were identified in 156 normal control chromosomes.
This study is the first confirmation that homozygous mutations in ADAMTSL4 are associated with autosomal recessive EL. The first compound heterozygous mutations are described. The identification of a causative mutation in ADAMTSL4 may allow exclusion of Marfan syndrome in these families and guide clinical management, of particular relevance in young children affected by EL.
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