In a large consanguineous Arab family of Jordanian origin with 15 affected individuals from four related sibships with autosomal recessive isolated ectopia lentis, Ahram et al. (2009) performed genome-wide linkage analysis and obtained a maximum multipoint lod score of 4.4 for marker D1S534 in the pericentromeric region on chromosome 1p13.2-q21.1. Fine mapping defined a 35-Mb critical region between markers D1S1675 and D1S498. Mutation screening for four candidate genes in the critical region of linkage resulted in the identification of homozygosity for a c.1785T>G transversion in exon 11 of the ADAMTSL4 gene, resulting in a tyr595-to-ter (Y595X) substitution at an evolutionarily conserved residue, predicted to generate a truncated protein of 594 residues lacking 6 of the 7 TSP1 repeats. The mutation was found to be segregated with the phenotype in the family and was not found in 380 ethnically matched control chromosomes. Ahram et al. (2009) concluded that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like 4 plays a role in the development and/or integrity of the zonular fibers.

[See: Jordan > Ahram et al., 2009].