Severe retinitis pigmentosa phenotype associated with novel CNGB1 variants
Abdulaziz A Alshamrani, Osama Raddadi, Patrik Schatz, Steffen Lenzner, Christine Neuhaus, Eman Azzam, Ehab Abdelkader, Abdulaziz A Alshamrani, Osama Raddadi, Patrik Schatz, Steffen Lenzner, Christine Neuhaus, Eman Azzam, Ehab Abdelkader
Abstract
Purpose: To report a severe phenotype of retinitis pigmentosa associated with novel mutations in CNGB1.
Observations: Six siblings, age range 50-75 years old, were examined using optical coherence tomography and fundus autofluorescene, electroretinogram testing, Goldman visual field testing, and genetic testing using next generation sequencing.In four affected siblings, two novel compound heterozygous variants in CNGB1 were detected: in exon 26 the missense variant c.2603G > A (p.(Gly868Asp)), and in exon 21, the in-frame 12-bp duplication c.2093_2104dupGCGACCTCATCT (p.(Cys698_lle701dup)). One sibling was unaffected and carried neither of the variants, while another sibling had mild macular degeneration changes and carried the latter variant in heterozygous status. The affected siblings presented with a phenotype showing markedly constricted visual field, flat scotopic and photopic electroretinogram responses and generalized retinal atrophy.
Conclusions and importance: This is the first report of a 12bp in-frame duplication and a missense variant (in compound heterozygous status) in CNGB1, being associated with a severe form of retinitis pigmentosa featuring extensive peripheral and central retinal degeneration. This study expands the molecular genetic basis of CNGB1-related disease.
Keywords: CNGB1; Novel variant; Retinitis pigmentosa; Rod-cone dystrophy.
© 2020 The Authors.
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References
- Hartong D.T., Berson E.L., Dryja T.P. Retinitis pigmentosa. Lancet. 2006 Nov 18;368(9549):1795–1809.
- Zheng J., Trudeau M.C., Zagotta W.N. Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit. Neuron. 2002 Dec 5;36(5):891–896.
- Kaupp U.B., Seifert R. Cyclic nucleotide-gated ion channels. Physiol Rev. 2002 Jul;82(3):769–824.
- Bocquet B., Marzouka N.A., Hebrard M. Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations. Mol Vis. 2013 Dec 8;19:2487–2500.
- Bareil C., Hamel C.P., Delague V., Arnaud B., Demaille J., Claustres M. Segregation of a mutation in CNGB1 encoding the beta-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa. Hum Genet. 2001 Apr;108(4):328–334.
- Marmor M.F., Zrenner E. Standard for clinical electroretinography. Doc Ophthalmol. 1995;97:143–156.
- Hull S., Attanasio M., Arno G. Clinical Characterization of CNGB1-Related Autosomal Recessive Retinitis Pigmentosa. JAMA Ophthalmol. 2017 Feb;135(2):137–144.
- Petersen-Jones S.M., Occelli L.M., Winkler P.A. Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach. J Clin Invest. 2018 Jan 2;128(1):190–206.
Source: PubMed