Genetic linkage of Bietti crystallin corneoretinal dystrophy to chromosome 4q35

Abstract

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal degeneration characterized by multiple glistening intraretinal dots scattered over the fundus, degeneration of the retina, and sclerosis of the choroidal vessels, ultimately resulting in progressive night blindness and constriction of the visual field. Although BCD has been associated with abnormalities in fatty-acid metabolism and absence of fatty-acid binding by two cytosolic proteins, the genetic basis of BCD is unknown. We report linkage of the BCD locus to D4S426 (maximum LOD score [Z(max)] 4.81; recombination fraction [straight theta] 0), D4S2688 (Zmax=3.97; straight theta=0), and D4S2299 (Zmax=5.31; straight theta=0), on chromosome 4q35-4qtel. Multipoint analysis confirmed linkage to the region telomeric of D4S1652 with a Z(max) of 5.3 located 4 cM telomeric of marker D4S2930.

Figures

Figure 1

Haplotypes for 10 markers from 4q35-4qtel, for 10 families with BCD. Marker order is shown to the left of each generation. Shading indicates haplotypes, with alleles of uncertain origin shaded to maximize the critical region. Families 2, 5, and 7 are all first-cousin matings, and, in these families, haplotypes consistent with identity by descent are shaded in solid black.