Details

Autor(en) / Beteiligte

• Hull, Sarah
• Arno, Gavin
• Ostergaard, Pia
• Pontikos, Nikolas
• Robson, Anthony G.
• Webster, Andrew R.
• Hogg, Chris R.
• Wright, Genevieve A.
• Henderson, Robert H.H.
• Martin, Carol-Anne
• Jackson, Andrew P.
• Mansour, Sahar
• Moore, Anthony T.
• Michaelides, Michel

Titel

Clinical and Molecular Characterization of Familial Exudative Vitreoretinopathy Associated With Microcephaly

Ist Teil von

• American journal of ophthalmology, 2019-11, Vol.207, p.87-98

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Familial exudative vitreoretinopathy (FEVR) is a rare finding in patients with genetic forms of microcephaly. This study documents the detailed phenotype and expands the range of genetic heterogeneity. Retrospective case series. Twelve patients (10 families) with a diagnosis of FEVR and microcephaly were ascertained from pediatric genetic eye clinics and underwent full clinical assessment including retinal imaging. Molecular investigations included candidate gene Sanger sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). All patients had reduced vision and nystagmus. Six were legally blind. Two probands carried bi-allelic LRP5 variants, both presenting with bilateral retinal folds. A novel homozygous splice variant, and 2 missense variants were identified. Subsequent bone density measurement identified osteoporosis in one proband. Four families had heterozygous KIF11 variants. Two probands had a retinal fold in one eye and chorioretinal atrophy in the other; the other 2 had bilateral retinal folds. Four heterozygous variants were found, including 2 large deletions not identified on Sanger sequencing or WES. Finally, a family of 2 children with learning difficulties, abnormal peripheral retinal vasculogenesis, and rod-cone dystrophy were investigated. They were found to have bi-allelic splicing variants in TUBGCP6. Three families remain unsolved following WES and WGS. Molecular diagnosis has been achieved in 7 of 10 families investigated, including a previously unrecognized association with LRP5. WGS enabled molecular diagnosis in 3 families after prior negative Sanger sequencing of the causative gene. This has enabled patient-specific care with targeted investigations and accurate family counseling. •All patients had reduced vision and nystagmus and half were legally blind.•Retinal findings ranged from peripheral non-perfusion to total retinal detachment.•Systemic associations included low bone density and learning difficulties.•Variants in LRP5, KIF11, and TUBGCP6 were identified in 7 of 10 families.