Genotype-phenotype correlation and longitudinal course in ten families with Best vitelliform macular dystrophy

Wabbels, Bettina; Preising, Markus N.; Kretschmann, Ulf; Demmler, Anke; Lorenz, Birgit

doi:10.1007/s00417-006-0286-6

Cited by 79 publications

(77 citation statements)

References 32 publications

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“…2,16,25,31 It was not possible to differentiate mutation carriers from non-mutation carriers in our cohort on the basis of EOG alone, and therefore genetic screening remains the mainstay for diagnosis of VMD. We did have a small number of patients (17%) with normal EOGs despite having a BEST1 mutation.…”

Section: Mutationmentioning

confidence: 92%

“…32,40,44 Wabbels and colleagues describe two separate families with reduced penetrance and late disease onset with BEST1 mutations of Ile295del and Asn99Lys. 2 Within our cohort, there were no such families with a preponderance of asymptomatic individualsFrather most families had a spectrum of disease severityFwith some unaffected mutation carriers balanced by others who were clearly affected ( Table 3). As with many other clinical studies of diseases with variable penetrance and expressivity, there was a wide inter-and intra-familial variability in the severity of disease manifestation.…”

Section: Mutationmentioning

confidence: 93%

“…[2][3][4] Most cases are due to mutations in the bestrophin 1 gene (BEST1; formerly named VMD2) located on chromosome 11q12-q13. Although the precise role of the encoded protein is still debated, bestrophin 1 is thought to belong to a family of calcium-activated chloride channels, [5][6][7][8] and has been identified on the basolateral plasma membrane of retinal pigment epithelium (RPE).…”

mentioning

confidence: 99%

“…However, VMD has known disease phenotypic variability and onset may be as late as the fifth decade. 2,[23][24][25][26] Typically, patients present with blurred vision, loss of central acuity or metamorphopsia. 24 The electrophysiological hallmark of VMD is a reduced Arden index on electro-oculogram (EOG).…”

mentioning

confidence: 99%

“…29,30 In the absence of genetic testing, the carrier state may often only be identified in VMD by an abnormal EOG; 29 however, some studies have shown the preservation of a normal EOG despite the presence of a BEST1 mutation. 2,16,25,31 Considerable variation in VMD disease expressivity has been observed. 16,26,[32][33][34][35] The funduscopic appearance of VMD varies depending on disease severity and stage.…”

mentioning

confidence: 99%

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Best's macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations

Cohn

Turnbull

Ruddle

et al. 2010

Eye

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Purpose (1) To evaluate the spectrum of BEST1 mutations within Australian Best Disease or vitelliform macular dystrophy (VMD) pedigrees, including any novel mutations; (2) to analyse the range of clinical presentations of this cohort; (3) to determine any possible genotype-phenotype correlations and (4) to compare clinical data of patients with phenotypic VMD, both with and without a BEST1 mutation. Patients and methods Patients with suspected VMD were referred to clinical centres for ophthalmological assessment and genetic screening. When a mutation was identified in a proband, further family members were invited for clinical and genetic screening. Results We identified 42 patients with one of 13 BEST1 mutations. Seven mutations were novel. There were a further 14 probands in whom a BEST1 mutation was not identified. Median visual acuity in both VMD (mutation positive) and clinical VMD (no BEST1 mutation identified) groups reached driving standards (6/12 or better). Conclusion We did not identify any firm genotype-phenotype correlations in our Australian VMD pedigrees, in which there was a spectrum of BEST1 mutations and marked variation in clinical presentation. Genetic screening remains the gold standard for VMD diagnosis. Patients should be counselled that visual acuity might remain at or above driving standards in at least one eye even in the presence of a BEST1 mutation.

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Section: Mutationmentioning

confidence: 92%

Section: Mutationmentioning

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Best's macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations

Cohn

Turnbull

Ruddle

et al. 2010

Eye

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Clinical and Genetic Heterogeneity in Multifocal Vitelliform Dystrophy

Boon

Klevering²,

Hollander³

et al. 2007

Arch Ophthalmol

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To describe the clinical and genetic findings in 15 patients with multifocal vitelliform lesions.Methods: All patients and, if possible, affected family members underwent an ophthalmic examination and their genomic DNA was analyzed for mutations in the vitelliform macular dystrophy 2 (VMD2) gene. Patients who did not have a mutation in the VMD2 gene were screened for mutations in the peripherin/RDS gene.Results: Patient age at onset of the disease was highly variable, ranging from 5 to 59 years. The peripheral lesions varied in number, size, and overall appearance but showed similar characteristics at autofluorescence imaging and optical coherence tomography compared with the central vitelliform lesion. Mutations in the VMD2 gene were identified in 9 of 15 patients. One patient without a VMD2 mutation carried a sequence variant in the 5Ј untranslated region of the peripherin/RDS gene.Conclusions: Multifocal vitelliform dystrophy is a clinically and genetically heterogeneous retinal disease that can be caused by mutations in the VMD2 gene. Other genes associated with this phenotype remain to be identified.Clinical Relevance: Clinical and molecular genetic characterization of multifocal vitelliform dystrophy may lead to better understanding of the pathophysiological mechanisms underlying this phenotype and may enable a more accurate prognosis in individual patients.

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Phenotypic Variability Due to a Novel Glu292Lys Variation in Exon 8 of the BEST1 Gene Causing Best Macular Dystrophy

Sohn¹

2009

Arch Ophthalmol

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Genotype-phenotype correlation and longitudinal course in ten families with Best vitelliform macular dystrophy

Cited by 79 publications

References 32 publications

Best's macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations

Best's macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations

Clinical and Genetic Heterogeneity in Multifocal Vitelliform Dystrophy

Phenotypic Variability Due to a Novel Glu292Lys Variation in Exon 8 of the BEST1 Gene Causing Best Macular Dystrophy

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