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. 1998 Oct;82(10):1162–1168. doi: 10.1136/bjo.82.10.1162

Phenotype of a British North Carolina macular dystrophy family linked to chromosome 6q

M Reichel 1, R Kelsell 1, J Fan 1, C Gregory 1, K Evans 1, A Moore 1, D Hunt 1, F Fitzke 1, A Bird 1
PMCID: PMC1722392  PMID: 9924305

Abstract

AIMS—To document the phenotype of an autosomal dominant macular dystrophy diagnosed as having North Carolina macular dystrophy (NCMD) in this British family, and to verify that the disease locus corresponds with that of MCDR1 on chromosome 6q.
METHODS—37 family members were examined and the phenotype characterised. DNA samples from the affected members, 19 unaffected and five spouses, were used to perform linkage analysis with six microsatellite marker loci situated within the MCDR1 region of chromosome 6q.
RESULTS—Every affected family member had lesions characteristic of NCMD, which developed early in life and usually remain stable thereafter. Although fundus changes are evident in the periphery, all tests revealed that functional loss is restricted to the macula. Some patients with large macular lesions had good visual acuity with fixation at the edge of the lesion at 5° eccentricity. Significant linkage to the MCDR1 locus on chromosome 6q was obtained with three marker loci, with a maximum lod score of 5.9 (q = 0.00) obtained with D6S249.
CONCLUSION—This family has the typical phenotype NCMD, and the causative gene was linked to the disease locus (MCDR1) on chromosome 6q. Early onset and localisation of the disease to the central macula allow specialisation of eccentric retina in some eyes with resultant good visual acuity.

 Keywords: macular dystrophy; linkage analysis; psychophysics

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Figure 1  .

Figure 1  

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Pedigree and haplotype results of six microsatellite marker loci situated on chromosome 6q. Solid symbols indicate affected and open symbols indicate unaffected members of the family. Slashed symbols show deceased individuals. The brackets indicate inferred haplotypes for individuals II-1, II-2, II-13, and III-3. The heavy line indicates the haplotype that appears segregate with disease (a small slash indicates where the phase of the alleles is uncertain). Recombinant IV-13 localises the disease gene telomeric to D6S251 and recombinant III-8 localises the disease gene centromeric to D6S468.

Figure 2  .

Figure 2  

Figure 2  

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A grade I lesion with drusen-like changes in the macular of patient III-8 (A). In the periphery are radial alignment of white dots (B). Patient IV-8 had a grade I lesion in the left eye (C), and a grade II lesion in the right (D). Grade III lesion in patient V-2 showing well demarcated chorioretinal atrophy at the macula, with white fibrous tissue and pigmentation on the edge of the lesion (E, F). An overlay of the SLO guided fixation test and the fundus photography reveals left eye fixation at the nasal rim of the macular lesion at about 5° of eccentricity (G).

Figure 3  .

Figure 3  

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Fine matrix mapping on the left eye of patient IV-8 with a grade II lesion shows up to 3 log units sensitivity loss (A), the right eye with a grade I has normal sensitivities (B). In patient V-2 with a grade III lesion, perimetric tests show a sharply demarcated central sensitivity loss of up to 20 dB in the scotopic (C) and photopic function (D) and displacement of the blind spot. There was marked sensitivity loss on fine matrix mapping (E). Dark adaptation curve reveals elevated prebleach sensitivities at the edge of the scotoma (closed symbols), normal sensitivities at 9° (open symbols), and normal recovery kinetics (F).

Selected References

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