Scanga Hannah L, Nischal Ken K
Division of Pediatric Ophthalmology, Strabismus, and Adult Motility, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
UPMC Eye Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Am J Med Genet A. 2022 Jun;188(6):1853-1857. doi: 10.1002/ajmg.a.62698. Epub 2022 Feb 26.
Pathogenic variants of ADAMTSL4 are associated with autosomal recessive ectopia lentis et pupillae and isolated ectopia lentis, often presenting congenitally or in childhood. We describe a pedigree of a 4-year-old female child with bilateral ectopia lentis and her asymptomatic 35-year-old father with mild anterior segment findings. Molecular evaluation revealed compound heterozygosity for ADAMTSL4 pathogenic variants in the proband and homozygosity for an ADAMTSL4 pathogenic founder mutation in her father. The results of genetic testing revealed a pseudodominant inheritance pattern in the family. This case expands variability of ADAMTSL4-related ectopia lentis through the first description of an asymptomatic adult in the 4th decade and highlights importance of clinical and molecular evaluations of family members when investigating genetic disorders.
ADAMTSL4的致病性变异与常染色体隐性晶状体异位和瞳孔异位以及孤立性晶状体异位相关,这些病症通常在先天性或儿童期出现。我们描述了一名患有双侧晶状体异位的4岁女童及其无症状的35岁父亲的家系,该父亲有轻度眼前节表现。分子评估显示,先证者为ADAMTSL4致病性变异的复合杂合子,其父亲为ADAMTSL致病奠基者突变的纯合子。基因检测结果显示该家族存在假显性遗传模式。本病例通过首次描述一名40岁无症状成年人,扩展了ADAMTSL4相关晶状体异位的变异性,并强调了在调查遗传疾病时对家庭成员进行临床和分子评估的重要性。