The gene responsible for autosomal dominant Doyne's honeycomb retinal dystrophy (DHRD) maps to chromosome 2p16 [published erratum appears in Hum Mol Genet 1996 Sep;5(9):1390]

Abstract

Degeneration in the macula region of the retina is a feature of a heterogeneous group of inherited, progressive disorders, causing blinding visual impairment. Autosomal dominant Doyne's honeycomb retinal dystrophy (DHRD) is characterised by the presence of drusen deposits at the level of Bruch's membrane in the macula and around the edge of the optic nerve head. We have studied 63 members of a large, nine-generation British pedigree by linkage analysis. Two-point analysis showed significant linkage to nine markers on the short arm of chromosome 2, a region overlapping that recently reported to be linked to Malattia leventinese. A maximum lod score (Zmax) of 7.29 (theta = 0.0) was obtained at marker locus D2S2251. Haplotype analysis of recombination events localised the disease to a 5 cM region between marker loci D2S2316 and D2S378. Striking clinical similarities between DHRD and the more common condition age-related macular degeneration (ARMD) suggest that the disease gene at this locus could be considered as the most likely candidate in future studies on ARMD.

Symptomatic abnormalities of dark adaptation in patients with EFEMP1 retinal dystrophy (Malattia Leventinese/Doyne honeycomb retinal dystrophy)

“…The confluent central deposits appear to occur as a secondary phenomenon, due possibly to the failure of material discharged from the retinal pigment epithelium to pass freely to the choroid through an abnormal Bruch's membrane. This pattern is consistently visible in some reported dominant drusen families [4][5][6][7]15,[22][23][24] but is not present in others. 11,12,15,[41][42][43][44][45][46][47][48][49] This phenotype has now been demonstrated in both ML and DHRD and is associated with the EFEMP1 mutation.…”

“…[18][19][20] Subsequent descriptions show that they may occur in a small number of members of the Doyne family, but are not prominent. 21 Despite these discrepancies, genes from ML and DHRD families colocalise 22,23 and a single EFEMP1 (EGF containing fibrillin-like extracellular matrix protein 1) mutation is associated with both disorders. 24 We wish to report six patients with EFEMP1 retinal dystrophy (ML/DHRD) who presented with subjective visual loss in association with diffuse peripapillary and macular drusen and associated radially-orientated peripheral drusen.…”

Genomic Mapping of Chromosomal Region 2p15–p21 (D2S378–D2S391): Integration of Genemap'98 within a Framework of Yeast and Bacterial Artificial Chromosomes

“…126600). These diseases, which had both been mapped to 2p16 (Edwards et al, 1998;Gregory et al, 1996;Heon et al, 1996;Kermani et al, 1999), were recently shown to be due to mutations in the EFEMP1 gene (Stone et al, 1999). Also, an overlapping interval on 2p15-p16 has been reported to contain a new locus for inherited dyslexia, designated DYX-3 (Fagerheim et al, 1998).…”

A new locus for dominant drusen and macular degeneration maps to chromosome 6q14

“…Despite some clinical differences, the two disorders are currently recognized as being identical at the genetic level. This conclusion was reached after the mapping of both to the same region on chromosome 2p, [3][4][5] and the subsequent cloning of the gene and characterization of the same mutation in all patients. 6 Another dominant form of age-related macular degeneration with drusen was mapped to chromosome 1q25-q31 in a US family.…”