Genetic Analysis of Color Vision Defects in Duchenne Muscular Dystrophy and Leber's Hereditary Optic Neuropathy

Abstract

Purpose: : 8-10% of males have an inherited red-green color vision defect and ~17% of females are carriers. The primary cause is rearrangements in the X-chromosome array of long (L) and middle (M) wavelength cone opsin genes. Patients with Duchenne Muscular Dystrophy (DMD) and asymptomatic carriers of Leber's Hereditary Optic Neuropathy (LHON) in a large Brazilian family have higher than expected frequencies of red-green color vision abnormalities. 66% of males with a dystrophin gene deletion affecting the retina isoform, Dp260, had color vision abnormalities, and males with a deletion that did not affect Dp260 had normal color vision. In the large Brazilian family, 49% of asymptomatic carriers of the LHON 11778 mitochondrial DNA (mtDNA) mutation had color vision abnormalities. The purpose of this study is to determine whether the high prevalence of color vision abnormalities in these patients can be attributed to their disease or to a familial cluster of an inherited red-green color vision deficiency.

Methods: : Real time quantitative polymerase chain reaction was used to estimate the relative number of L and M cone opsin genes in 28 males with DMD, and in 11 affected and 13 asymptomatic carriers of LHON from the large Brazilian family.

Results: : Of the 16 DMD males with a deletion affecting Dp260, all had X-chromosome opsin gene arrays characteristic of normal color vision, and of 12 with deletions that did not affect Dp260, 2 had arrays with multiple L opsin genes, characteristic of deutan defects. Of the 13 asymptomatic carriers of LHON, 5 of 7 males had characteristic deutan opsin gene arrays and 5 of 6 females had arrays with a high proportion of L opsin genes, characteristic of female carriers of deutan defects. Four of 9 males with LHON had characteristic deutan opsin gene arrays, and 2 of 2 affected females had arrays characteristic of deutan carriers.

Conclusions: : 7% of the DMD males had an inherited color vision defect, consistent with the population frequency of these defects, thus color vision abnormalities in DMD are related to the disease. 77% of asymptomatic LHON carriers either had or carried an inherited deutan defect. The association between color vision loss and LHON can be determined by analysis of individuals with the LHON mtDNA but without the inherited deutan defect.

Keywords: color vision • genetics • visual impairment: neuro-ophthalmological disease