Date Published:
2022 Dec
Abstract:
A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in the
PDE6B gene in the affected twins and their unaffected father. Further investigation, using genome sequencing, identified a novel ∼7.5-kb deletion (Chr 4:670,405-677,862del) encompassing the
ATP5ME gene, part of the 5' UTR of
MYL5, and a 378-bp (Chr 4:670,405-670,782) region from the 3' UTR of
PDE6B in the affected twins and their unaffected mother. Both variants segregated with disease in the family. Analysis of the relative expression of
PDE6B, in peripheral blood cells, also revealed a significantly lower level of
PDE6B transcript in affected siblings compared to a normal control.
PDE6B is associated with recessive rod-cone degeneration and autosomal dominant congenital stationary night blindness. Ophthalmic evaluation of these patients showed night blindness, fundus abnormalities, and peripheral vision loss, which are consistent with
PDE6B-associated recessive retinal degeneration. These findings suggest that the loss of
PDE6B transcript resulting from the compound heterozygous pathogenic variants is the underlying cause of recessive rod-cone degeneration in the study family.
