A homozygous microdeletion within ADAMTSL4 in patients with isolated ectopia lentis: evidence of a founder mutation.

PURPOSE The purpose of the study was to look for ADAMTSL4 mutations in a cohort of German patients with isolated ectopia lentis from nonconsanguineous families. METHODS Mutation screening was performed by PCR amplification of the coding exons of ADAMTSL4 and subsequent sequencing. RESULTS An identical homozygous deletion of 20 bp of coding sequence within exon 6 (NM_019032.4:c.759_778del20) was identified in eight individuals from seven unrelated families. In a screen of 360 ethnically matched, unaffected individuals, two heterozygous mutation carriers were found. The mutation was always accompanied by the identical haplotype, suggestive of a founder mutation. CONCLUSIONS The results emphasize the association of ADAMTSL4 null mutations with isolated ectopia lentis and the presence of a founder mutation in the European population. Screening of ADAMTSL4 should be considered in all patients with isolated ectopia lentis, with or without family history. In patients from nonconsanguineous families, the authors propose a two-step diagnostic approach, starting with an examination of exon 6 before sequencing the entire coding region of ADAMTSL4.