Novel <i>ADAMTSL4</i> gene mutations in Chinese patients with isolated ectopia lentis.

Abstract

To characterise the phenotype and genetic defects of isolated ectopia lentis (IEL) and to determine the <i>ADAMTSL4</i> gene mutation frequencies in a Chinese congenital ectopia lentis (CEL) cohort. In total, 127 Chinese probands with a clinical CEL diagnosis were recruited for this study and underwent ocular and systemic examinations. Whole-exome sequencing was used to detect variants, and Sanger sequencing and bioinformatics analysis verified the pathogenic mutations. Overall, biallelic mutations in <i>ADAMTSL4,</i> involving 8 novel <i>ADAMTSL4</i> mutations (c.21-2A>G, c.1174G>C, c.2169C>A, c.2236C>T, c.2263delG, c.2397C>A, c.2488dupC and c.2935T>C) were identified in 5 probands (5/127, 3.94%) with IEL. Additionally, four patients had combined congenital cataracts, and two patients had ectopia lentis et pupillae (ELP). One of eight mutations was a homozygous missense mutation, and the other seven mutations were compound heterozygous. These eight consisted of three missense (37.5%), three frameshift (37.5%), one stop-gain (12.5%) and one spicing mutation (12.5%). These mutations co-segregated with the IEL, and the substitution of amino acids greatly affected conserved residues. Most of the novel mutations were located in the thrombospondin type 1 (TSP1) domain, which ultimately alters the structure of the ADAMTSL4 protein. This study reported five IEL probands with eight novel mutations in the <i>ADAMTSL4</i> gene. The clinical IEL phenotypes caused by these mutations were variable and complex. This study thus establishes the <i>ADAMTSL4</i> gene mutation frequency and expands the gene's mutation spectrum to help recognise <i>ADAMTSL4</i>-related IEL clinical manifestations.