Journal article
Genotype-phenotype spectrum in isolated and syndromic nanophthalmos.
- Lang E Department of Ophthalmology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Koller S Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland.
- Atac D Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland.
- Pfäffli OA Department of Ophthalmology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Hanson JVM Department of Ophthalmology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Feil S Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland.
- Bähr L Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland.
- Bahr A Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
- Kottke R Department of Diagnostic Imaging, University Children's Hospital Zurich, Zurich, Switzerland.
- Joset P Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
- Fasler K Department of Ophthalmology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Barthelmes D Department of Ophthalmology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Steindl K Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
- Konrad D Department of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland.
- Wille DA Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
- Berger W Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland.
- Gerth-Kahlert C Department of Ophthalmology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- 2020-09-30
Published in:
- Acta ophthalmologica. - 2020
English
PURPOSE
To (i) describe a series of patients with isolated or syndromic nanophthalmos with the underlying genetic causes, including novel pathogenic variants and their functional characterization and (ii) to study the association of retinal dystrophy in patients with MFRP variants, based on a detailed literature review of genotype-phenotype correlations.
METHODS
Patients with nanophthalmos and available family members received a comprehensive ophthalmological examination. Genetic analysis was based on whole-exome sequencing and variant calling in core genes including MFRP, BEST1, TMEM98, PRSS56, CRB1, GJA1, C1QTNF5, MYRF and FAM111A. A minigene assay was performed for functional characterization of a splice site variant.
RESULTS
Seven patients, aged between three and 65 years, from five unrelated families were included. Novel pathogenic variants in MFRP (c.497C>T, c.899-3C>A, c.1180G>A), and PRSS56 (c.1202C>A), and a recurrent de novo variant in FAM111A (c.1706G>A) in a patient with Kenny-Caffey syndrome type 2, were identified. In addition, we report co-inheritance of MFRP-related nanophthalmos and ADAR-related Aicardi-Goutières syndrome.
CONCLUSION
Nanophthalmos is a genetically heterogeneous condition, and the severity of ocular manifestations appears not to correlate with variants in a specific gene. However, retinal dystrophy is only observed in patients harbouring pathogenic MFRP variants. Furthermore, heterozygous carriers of MFRP and PRSS56 should be screened for the presence of high hyperopia. Identifying nanophthalmos as an isolated condition or as part of a syndrome has implications for counselling and can accelerate the interdisciplinary care of patients.
To (i) describe a series of patients with isolated or syndromic nanophthalmos with the underlying genetic causes, including novel pathogenic variants and their functional characterization and (ii) to study the association of retinal dystrophy in patients with MFRP variants, based on a detailed literature review of genotype-phenotype correlations.
METHODS
Patients with nanophthalmos and available family members received a comprehensive ophthalmological examination. Genetic analysis was based on whole-exome sequencing and variant calling in core genes including MFRP, BEST1, TMEM98, PRSS56, CRB1, GJA1, C1QTNF5, MYRF and FAM111A. A minigene assay was performed for functional characterization of a splice site variant.
RESULTS
Seven patients, aged between three and 65 years, from five unrelated families were included. Novel pathogenic variants in MFRP (c.497C>T, c.899-3C>A, c.1180G>A), and PRSS56 (c.1202C>A), and a recurrent de novo variant in FAM111A (c.1706G>A) in a patient with Kenny-Caffey syndrome type 2, were identified. In addition, we report co-inheritance of MFRP-related nanophthalmos and ADAR-related Aicardi-Goutières syndrome.
CONCLUSION
Nanophthalmos is a genetically heterogeneous condition, and the severity of ocular manifestations appears not to correlate with variants in a specific gene. However, retinal dystrophy is only observed in patients harbouring pathogenic MFRP variants. Furthermore, heterozygous carriers of MFRP and PRSS56 should be screened for the presence of high hyperopia. Identifying nanophthalmos as an isolated condition or as part of a syndrome has implications for counselling and can accelerate the interdisciplinary care of patients.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1111/aos.14615
- PMID 32996714
- Persistent URL
- https://folia.unifr.ch/global/documents/110346
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