One hundred thirty-eight patients with retinopathies, including 34
autosomal dominant retinitis pigmentosa, 43 autosomal recessive
retinitis pigmentosa, 20 cone–rod dystrophy, 11 Usher syndrome, and
others, including Leber congenital amaurosis, Stargardt disease, Best
disease, and congenital stationary night blindness, were screened for
mutations in the
HRG4 gene. A patient with a heterozygous
A-to-T transition in codon 57, changing a lysine to a premature
termination codon, was identified (
Fig. 1A ). The position of this mutation was precisely at the border between
the putative proximal and distal domains of the 240-amino-acid HRG4
protein.
10 This mutation was not present in 100 unaffected
individuals. A polymorphic variant (C to T) was also identified in the
3′ noncoding region of the gene (position 778 in the cDNA sequence) at
a frequency of 29%. The patient, who had had symptoms of poor night
vision, defective color vision, and light sensitivity from age 40, at
age 57 years had reduced visual acuity (20/40), myopia, macular
atrophy, pericentral ring scotomas, and an electroretinogram (ERG)
consistent with cone–rod dystrophy
(Figs. 1B 1C 1D) . A
36-year-old daughter carrying the same mutation had a history of seeing
bright flashes from a young age, as was also experienced by her mother
(proband), but does not yet demonstrate clear-cut ERG abnormalities,
probably because of her young age for a late-onset disease. An older
son and a daughter who do not carry the mutation have normal vision.