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Genotype-Phenotype Analysis of a Novel Recessive and a Recurrent Dominant SNRNP200 Variant Causing Retinitis Pigmentosa


Gerth-Kahlert, Christina; Koller, Samuel; Hanson, James V M; Baehr, Luzy; Tiwari, Amit; Kivrak-Pfiffner, Fatma; Bahr, Angela; Berger, Wolfgang (2019). Genotype-Phenotype Analysis of a Novel Recessive and a Recurrent Dominant SNRNP200 Variant Causing Retinitis Pigmentosa. Investigative Ophthalmology & Visual Science [IOVS], 60(8):2822-2835.

Abstract

Purpose

To compare phenotype variability in retinitis pigmentosa patients with recessive and dominant mutations in the SNRNP200 gene.

Methods

In a retrospective study, patients of two unrelated families were identified: family A, five patients aged 36 to 77 years; family B, one patient aged 9 years and his asymptomatic parents and sister. All patients received a comprehensive eye examination with a detailed retinal functional and morphologic assessment. Genetic testing was performed by whole exome sequencing (WES) in the index patient from each family. Genes described to be involved in eye diseases (n > 450) were screened for rare variants and segregation analysis was performed.

Results

A known heterozygous missense variant (c.3260C>T, p.(Ser1087Leu)) in the SNRNP200 gene was identified in the index patient of family A while a novel homozygous missense mutation (c.1634G>A, p.(Arg545His)) was found in the index patient of family B. Nyctalopia and photophobia were reported by 6/6 and 2/6 patients, respectively. The phenotype associated with the dominant mutation was characterized by variable disease onset (early childhood to the sixth decade of life), disease severity (visual acuity of 20/20-20/200 in the seventh to eighth decade), and advanced rod-cone dysfunction. Characteristics of recessive disease included distinct fundus changes of dot-like hypopigmentation together with retinal atrophy and severe rod-cone dysfunction.

Conclusions

The phenotype characteristics in autosomal dominant and recessive SNRNP200 mutations show distinct features, with earlier severe disease in the recessive case and a variable disease expression in the dominant inheritance pattern.

Abstract

Purpose

To compare phenotype variability in retinitis pigmentosa patients with recessive and dominant mutations in the SNRNP200 gene.

Methods

In a retrospective study, patients of two unrelated families were identified: family A, five patients aged 36 to 77 years; family B, one patient aged 9 years and his asymptomatic parents and sister. All patients received a comprehensive eye examination with a detailed retinal functional and morphologic assessment. Genetic testing was performed by whole exome sequencing (WES) in the index patient from each family. Genes described to be involved in eye diseases (n > 450) were screened for rare variants and segregation analysis was performed.

Results

A known heterozygous missense variant (c.3260C>T, p.(Ser1087Leu)) in the SNRNP200 gene was identified in the index patient of family A while a novel homozygous missense mutation (c.1634G>A, p.(Arg545His)) was found in the index patient of family B. Nyctalopia and photophobia were reported by 6/6 and 2/6 patients, respectively. The phenotype associated with the dominant mutation was characterized by variable disease onset (early childhood to the sixth decade of life), disease severity (visual acuity of 20/20-20/200 in the seventh to eighth decade), and advanced rod-cone dysfunction. Characteristics of recessive disease included distinct fundus changes of dot-like hypopigmentation together with retinal atrophy and severe rod-cone dysfunction.

Conclusions

The phenotype characteristics in autosomal dominant and recessive SNRNP200 mutations show distinct features, with earlier severe disease in the recessive case and a variable disease expression in the dominant inheritance pattern.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Ophthalmology Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Reconstructive Surgery
04 Faculty of Medicine > Institute of Medical Molecular Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Ophthalmology
Life Sciences > Sensory Systems
Life Sciences > Cellular and Molecular Neuroscience
Language:English
Date:1 July 2019
Deposited On:07 Jan 2020 10:58
Last Modified:28 Oct 2020 08:04
Publisher:Association for Research in Vision and Ophthalmology
ISSN:0146-0404
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1167/iovs.18-25643
PubMed ID:31260034

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