Compound Heterozygous Inheritance of Best Vitelliform Macular Dystrophy

Abstract

Purpose: : In 2006, Schatz et al., reported two family members with Best vitelliform macular dystrophy (BVMD) associated with compound heterozygous mutations in BEST1. The purpose of this work was to identify and characterize individuals with compound heterozygous BVMD.

Methods: : Blood samples were obtained from 195 unrelated individuals with the clinical findings of BVMD and screened for mutations in BEST1. Informed consent was obtained from all individuals, or from their legal guardians, in accordance with the Declaration of Helsinki. All individuals were examined clinically and the presence or absence of phenotypic BVMD was assessed.

Results: : Ten of the 195 individuals screened were found to have two plausible disease-causing variations in the BEST1 gene. Phase was determined in one extended pedigree in which two first cousins were clinically affected with BVMD. These cousins were both found to harbor a Pro152Ala mutation, but differed in their second allele (Arg141His and Ile201Thr). Other unrelated probands were found to harbor the following allele combinations: (Leu88 del17cTGGTCGTGACCCGCTGG and Ala195Val GCG>GTG), (Ile201Thr and 3bp del codon 281), (Pro274Cys and IVS7-2 A>G), and one proband was found to be homozygous for Ile205 del12 atCCTGCTCCAGAG. The parents of the compound heterozygous patients did not show clinical evidence of BVMD, and there were no other known affected relatives.

Conclusions: : The data presented here provide additional evidence that two abnormal BEST1 alleles, neither of which causes BVMD alone, can act in concert to cause the disease.

Keywords: genetics • mutations • retinal degenerations: hereditary