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Clinical and molecular characterization of familial exudative vitreoretinopathy associated with microcephaly
- Source :
- Hull, S, Arno, G, Ostergaard, P, Pontikos, N, Robson, A G, Webster, A R, Hogg, C R, Wright, G A, Henderson, R H H, Martin, C-A, Jackson, A P, Mansour, S, Moore, A T & Michaelides, M 2019, ' Clinical and molecular characterization of familial exudative vitreoretinopathy associated with microcephaly ', American journal of ophthalmology . https://doi.org/10.1016/j.ajo.2019.05.001
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- PURPOSE: 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. Design; Retrospective case-series METHODS: Twelve patients (ten 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).RESULTS: 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 two 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 two had bilateral retinal folds. Four heterozygous variants were found, including two large deletions not identified on Sanger sequencing or WES.Finally, a family of two 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.CONCLUSIONS: Molecular diagnosis has been achieved in seven of ten families investigated including a previously unrecognized association with LRP5. WGS enabled molecular diagnosis in three families after prior negative Sanger sequencing of the causative gene. This has enabled patient-specific care with targeted investigations and accurate family counseling.
- Subjects :
- Proband
Male
Candidate gene
Microcephaly
Adolescent
Fundus Oculi
Familial Exudative Vitreoretinopathies
DNA Mutational Analysis
Kinesins
03 medical and health sciences
symbols.namesake
chemistry.chemical_compound
0302 clinical medicine
medicine
Electroretinography
Missense mutation
Humans
Abnormalities, Multiple
Fluorescein Angiography
Child
030304 developmental biology
Retrospective Studies
Sanger sequencing
Genetics
0303 health sciences
Genetic heterogeneity
business.industry
Infant
Retinal
DNA
medicine.disease
Pedigree
Ophthalmology
Low Density Lipoprotein Receptor-Related Protein-5
Phenotype
chemistry
Child, Preschool
Mutation
030221 ophthalmology & optometry
Familial exudative vitreoretinopathy
symbols
Female
business
Microtubule-Associated Proteins
Tomography, Optical Coherence
Subjects
Details
- Language :
- English
- ISSN :
- 18791891
- Database :
- OpenAIRE
- Journal :
- Hull, S, Arno, G, Ostergaard, P, Pontikos, N, Robson, A G, Webster, A R, Hogg, C R, Wright, G A, Henderson, R H H, Martin, C-A, Jackson, A P, Mansour, S, Moore, A T & Michaelides, M 2019, ' Clinical and molecular characterization of familial exudative vitreoretinopathy associated with microcephaly ', American journal of ophthalmology . https://doi.org/10.1016/j.ajo.2019.05.001
- Accession number :
- edsair.doi.dedup.....2200afe95dbb50f27dfce171368a55e8