Bestrophinopathy: A spectrum of ocular abnormalities caused by the c.614T.C mutation in the BEST1 gene

Lisa Toto, Camiel J. F. Boon, Luca Di Antonio, Maurizio Battaglia Parodi, Rodolfo Mastropasqua, Ivana Antonucci, Liborio Stuppia, LiborioLeonardo Mastropasqua

Research output: Contribution to journalArticle

Abstract

Purpose: To describe the variable ocular phenotype associated with a heterozygous mutation in the BEST1 gene. Methods: Clinical and genetic assessment was performed in five members of the same family. Molecular genetic analysis of the BEST1 gene was performed by direct sequencing. Extensive ophthalmic examination included color fundus imaging, spectral domain optical coherence tomography, fundus autofluorescence, electro-oculography (EOG), and full-field electroretinography (ERG). The main outcome measures were BEST1 mutations, imaging, and electroretinography findings. Results: All affected family members carried a single heterozygous c.614T.C (p.I205T) mutation in exon 5 of the BEST1 gene. The 46-year-old proband showed nanophthalmos with chorioretinal atrophy in the macula, extensive coarse hyperpigmentation in the (mid) peripheral retina with tractional vitreous strands. Full-field ERG revealed nonrecordable cone and rod responses, and EOG showed an absent light rise. The daughter and son of the proband showed a phenotype resembling autosomal recessive bestrophinopathy, including short axial lengths, cystoid fluid collections, and shallow serous subretinal fluid accumulation on spectral domain optical coherence tomography throughout the macula in combination with mild retinal pigment epithelium changes. The son of the proband also showed subretinal yellowish deposits inferiorly in the macula as well as outside the temporal vascular arcade, that were hyperfluorescent on fundus autofluorescence, similar to those seen in autosomal recessive bestrophinopathy. Full-field ERG revealed a reduced rod and cone response and a markedly reduced or absent EOG light peak in both brother and sister of the proband. Conclusion: The clinical spectrum of bestrophinopathy may encompass severe ocular phenotypes that affect the development and function of the entire eye. A clinical picture similar to autosomal recessive bestrophinopathy can also be caused by a single heterozygous mutation in the BEST1 gene, such as the c.614T.C (p.I205T) variant in this family.
Original languageEnglish
Pages (from-to)1586 - 1595
Number of pages10
JournalRetina
Volume36
Issue number8
DOIs
Publication statusPublished - Jul 26 2016

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Eye Abnormalities
Electroretinography
Nuclear Family
Mutation
Vertebrate Photoreceptor Cells
Optical Coherence Tomography
Phenotype
Genes
Siblings
Subretinal Fluid
Light
Hyperpigmentation
Retinal Pigment Epithelium
Atrophy
Blood Vessels
Retina
Molecular Biology
Exons
Color
Outcome Assessment (Health Care)

Keywords

  • Autosomal inheritance
  • BEST1 gene
  • Bestrophinopathy

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Toto, L., Boon, C. J. F., Di Antonio, L., Parodi, M. B., Mastropasqua, R., Antonucci, I., ... Mastropasqua, L. (2016). Bestrophinopathy: A spectrum of ocular abnormalities caused by the c.614T.C mutation in the BEST1 gene. Retina, 36(8), 1586 - 1595. https://doi.org/10.1097/IAE.0000000000000950

Bestrophinopathy: A spectrum of ocular abnormalities caused by the c.614T.C mutation in the BEST1 gene. / Toto, Lisa; Boon, Camiel J. F.; Di Antonio, Luca; Parodi, Maurizio Battaglia; Mastropasqua, Rodolfo; Antonucci, Ivana; Stuppia, Liborio; Mastropasqua, LiborioLeonardo.

In: Retina, Vol. 36, No. 8, 26.07.2016, p. 1586 - 1595.

Research output: Contribution to journalArticle

Toto, L, Boon, CJF, Di Antonio, L, Parodi, MB, Mastropasqua, R, Antonucci, I, Stuppia, L & Mastropasqua, L 2016, 'Bestrophinopathy: A spectrum of ocular abnormalities caused by the c.614T.C mutation in the BEST1 gene', Retina, vol. 36, no. 8, pp. 1586 - 1595. https://doi.org/10.1097/IAE.0000000000000950
Toto, Lisa ; Boon, Camiel J. F. ; Di Antonio, Luca ; Parodi, Maurizio Battaglia ; Mastropasqua, Rodolfo ; Antonucci, Ivana ; Stuppia, Liborio ; Mastropasqua, LiborioLeonardo. / Bestrophinopathy: A spectrum of ocular abnormalities caused by the c.614T.C mutation in the BEST1 gene. In: Retina. 2016 ; Vol. 36, No. 8. pp. 1586 - 1595.
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AU - Parodi, Maurizio Battaglia

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