In 10 affected individuals from 5 Norwegian families with ectopia lentis et pupillae (225200), Christensen et al. (2010) identified homozygosity for a 20-bp deletion (767_786del20) in the ADAMTSL4 gene, causing a frameshift predicted to result in a stop codon and premature termination 113 bp downstream. RT-PCR analysis of ADAMTSL4 mRNA confirmed the presence of a transcript truncated by 20 bp. Obligate heterozygotes had no ocular abnormalities. Homozygosity mapping in the 5 Norwegian families from Hordaland County in western Norway was compatible with a common ancestor 150 generations (4,000 years) earlier, and the mutation was found in heterozygosity in 3 of 190 local blood donors, corresponding to a prevalence for homozygosity of approximately 1:16,000 in this population. In 1 family, 1 of the 3 affected individuals had bilateral downward dislocation of the lenses but normally positioned pupils.
In a 15-year-old boy with isolated ectopia lentis (ECTOL2; 252100), Aragon-Martin et al. (2010) identified homozygosity for the 20-bp deletion in exon 6 of the ADAMTSL4 gene. The 20-bp deletion was also identified in compound heterozygosity with an 11-bp deletion (826_836del11; 610113.0004) in ADAMTSL4 in 2 affected members of a Caucasian British family with ectopia lentis and in an 8-year-old Swedish boy with ectopia lentis et pupillae.
In 8 patients from 7 German families with isolated ectopia lentis, Neuhann et al. (2011) identified homozygosity for the 20-bp deletion in the ADAMTSL4 gene, which they designated 759_778del20. The mutation was found in heterozygosity in unaffected parents and sibs, as well as in 2 of 360 controls. A 4-SNP haplotype was consistently associated with the mutation, suggestive of a founder mutation.
In 6 Caucasian British patients with isolated ectopia lentis, Chandra et al. (2012) identified homozygosity for the ADAMTSL4 20-bp deletion (Gln256ProfsTer38). Two more Caucasian British patients, 1 with isolated ectopia lentis and 1 with ectopia lentis et pupillae, were found to be compound heterozygous for the 20-bp deletion and 2 different frameshift mutations: a 1-bp deletion (237delC, Pro80ArgfsTer53; 610113.0006) and a 1-bp duplication (2270dupG, Gly758TrpfsTer59; 610113.0007), respectively, in the ADAMTSL4 gene.
