AUTHOR=Zhang Min , Chen Zexu , Chen Tianhui , Sun Xiaodong , Jiang Yongxiang 

TITLE=Cysteine Substitution and Calcium-Binding Mutations in FBN1 cbEGF-Like Domains Are Associated With Severe Ocular Involvement in Patients With Congenital Ectopia Lentis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.816397

DOI=10.3389/fcell.2021.816397

ISSN=2296-634X

ABSTRACT=<p><bold>Purpose:</bold> To investigate the clinical manifestations of congenital ectopia lentis (CEL) in patients with fibrillin (<italic>FBN1</italic>) calcium-binding epidermal growth factor (cbEGF)-like mutations.</p><p><bold>Design:</bold> Retrospective cohort study.</p><p><bold>Methods:</bold> Consecutive 68 CEL probands with <italic>FBN1</italic> cbEGF-like mutations were recruited, mostly comprising Marfan syndrome (MFS) patients. Patients were classified into the cysteine group (<italic>n</italic> = 43), calcium (Ca<sup>2+</sup>)-binding group (<italic>n</italic> = 13) or the others (<italic>n</italic> = 12) according to their genotypes. Ocular biometrics, morbidities and visual performance were compared among different mutation groups. Linear regression was used to evaluate the risk factors for axial length (AL) elongation.</p><p><bold>Results:</bold> With age-adjustment, cysteine substitution and Ca<sup>2+</sup>-binding mutations positively contributed to AL elongation (standardized coefficient: 0.410 and 0.367, <italic>p</italic> = 0.008 and 0.017, respectively). In addition, cataract formation was more frequently detected in patients with Ca<sup>2+</sup>-binding mutations (observed <italic>n</italic> = 3, expected n = 1.0; <italic>p</italic> = 0.036). Patients with cysteine substitutions had the poorest preoperative visual acuity among the three groups (<italic>p</italic> = 0.012) and did not recover as well as other patients. More MFS diagnoses were made in patients with cysteine substitutions (observed <italic>n</italic> = 16, expected <italic>n</italic> = 12.6), while ectopia lentis syndrome was detected more often in patients with cbEGF-like mutations out of the functional regions (observed n = 6, expected n = 2.5; <italic>p</italic> = 0.023).</p><p><bold>Conclusion:</bold> Compared with patients with cbEGF-like mutations out of functional regions, patients with cysteine substitutions or Ca<sup>2+</sup>-binding mutations had longer ALs with age adjustment, poorer ocular involvement, visual performance, and systematic manifestations.</p>