Clinical evaluation of two consanguineous families with homozygous mutations in BEST1

To describe the clinical and genetic findings in two consanguineous families with Best vitelliform macular dystrophy (BVMD) and homozygous mutations in the bestrophin-1 (BEST1) gene. Ophthalmologic examination was performed in eight members of two families originating from Spain and Denmark. Mutatio...

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Bibliographic Details
Published in:	Molecular vision Vol. 17; no. 179; pp. 1607 - 1617
Main Authors:	Piñeiro-Gallego, Teresa, Álvarez, María, Pereiro, Inés, Campos, Severiano, Sharon, Dror, Schatz, Patrik, Valverde, Diana
Format:	Journal Article
Language:	English
Published:	United States Molecular Vision 2011
Subjects:	Bestrophins Biochemistry and Molecular Biology Biokemi och molekylärbiologi Biologi Biological Sciences Child Child, Preschool Chloride Channels - genetics Chloride Channels - metabolism Consanguinity Denmark Electrooculography Exons Eye Proteins - genetics Eye Proteins - metabolism Female Genetic Association Studies Genotype Heterozygote Homozygote Humans Male Mutation, Missense Natural Sciences Naturvetenskap Oligonucleotide Array Sequence Analysis Pedigree Phenotype Sequence Analysis, DNA Severity of Illness Index Spain Tomography, Optical Coherence Vitelliform Macular Dystrophy - genetics Vitelliform Macular Dystrophy - pathology
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Summary:	To describe the clinical and genetic findings in two consanguineous families with Best vitelliform macular dystrophy (BVMD) and homozygous mutations in the bestrophin-1 (BEST1) gene. Ophthalmologic examination was performed in eight members of two families originating from Spain and Denmark. Mutation screening was performed using the Vitelliform Macular Dystrophy mutation array from Asper Biotech, and by the directed genomic sequencing of BEST1. Two homozygous mutations were detected in these families. Mutation c.936C>A (p.Asp312Glu) has been reported previously in a Danish family; here, we describe four additional individuals in this family demonstrating findings compatible with a severe dominant BVMD, albeit with reduced penetrance in heterozygotes. In the Spanish family, a novel homozygous missense mutation in exon 4, c.388 C>A (p.Arg130Ser), was identified in the siblings. Homozygous siblings demonstrated evidence of multifocal vitelliform retinopathy, whereas heterozygous family members presented findings ranging from isolated reduction of the electrooculogram Arden ratio to normal values on all clinical parameters. As demonstrated in these consanguineous families, a great clinical variability is associated with homozygous mutations in BEST1, ranging from severe dominant BVMD with reduced penetrance in heterozygotes to autosomal recessive bestrophinopathy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1090-0535 1090-0535