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Role of ADAMTSL4 mutations in FBN1 mutation‐negative ectopia lentis patients
Author(s) -
AragonMartin Jose Antonio,
Ahnood Dana,
Charteris David G,
Saggar Anand,
Nischal Ken K,
Comeglio Paolo,
Chandra Aman,
Child Anne H,
Arno Gavin
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21305
Subject(s) - genetics , ectopia lentis , missense mutation , biology , proband , nonsense mutation , mutation , compound heterozygosity , sanger sequencing , exon , allele , marfan syndrome , gene , medicine , surgery
Ectopia lentis (EL) is genetically heterogeneous with both autosomal‐dominant and ‐recessive forms. The dominant disorder can be caused by mutations in FBN1 , at the milder end of the type‐1 fibrillinopathies spectrum. Recently in a consanguineous Jordanian family, recessive EL was mapped to locus 1q21 containing the ADAMTSL4 gene and a nonsense mutation was found in exon 11 (c.1785T>G, p.Y595X). In this study, 36 consecutive probands with EL who did not fulfill the Ghent criteria for MFS were screened for mutations in FBN1 and ADAMTSL4 . Causative FBN1 mutations were identified in 23/36 (64%) of probands while homozygous or compound heterozygous ADAMTSL4 mutations were identified in 6/12 (50%) of the remaining probands. Where available, familial screening of these families confirmed the mutation co‐segregated with the EL phenotype. This study confirms that homozygous mutations in ADAMTSL4 are associated with autosomal‐recessive EL in British families. Furthermore; the first compound heterozygous mutation is described resulting in a PTC and a missense mutation in the PLAC (protease and lacunin) domain. The identification of a causative mutation in ADAMTSL4 may allow the exclusion of Marfan syndrome in these families and guide the clinical management, of particular relevance in young children affected by EL. © 2010 Wiley‐Liss, Inc.