Novel RDH12 sequence variations in Leber congenital amaurosis

RDH12Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function

“…3,5,8,13,30,32,[36][37][38][39][40][41][42][43][44] There are examples of segregation of RHD12 mutations in an autosomal dominant fashion and several heterozygous mutations have been reported in patients with RP. 6,8,32,36,37,39,42 Instead of the phenotypic diversity implied by the different diagnoses used to describe the autosomal recessive disease, review of the literature reveals a consistent phenotype characterized by a midperipheral pigmentary retinopathy of early onset 3,8,13,28,36,37,45 and a maculopathy 5,8,13,28,30,33,[38][39][40][41] that includes macular pseudo-colobomas. 15,16,[30][31][32][33] Whereas there is a wealth of information on the retinal structure of the retinal degeneration associated with RDH12 mutations, details of the associated retinal dysfunction are comparatively scarce.…”

“…Limited longitudinal studies and multiple cross-sectional observations in patients with RHD12-associated IRD indicate visual acuity may be relatively preserved early in the course of the disease, while a somewhat steep decline occurs in the second decade of life, reaching count finger or LP level of vision by age 20. 3,8,14,[28][29][30][31][32]36,41,78 Relatively preserved visual acuity and even color vision, may be documented in RDH12-IRD despite severe central retinal disease and is still in keeping with a diagnosis of CRD. 32,37 Such pattern of early relative preservation of visual acuity and then rapid loss is reminiscent of numerous maculopathies that show preservation of visual acuity despite severe central retinal disease.…”

Natural History and Genotype-Phenotype Correlations in RDH12-Associated Retinal Degeneration

“…Overall, these data point to a rapidly progressive degenerative process that starts in early childhood, before the age of 5, and generally progresses throughout childhood and adolescence to severe vision loss by the age of 20 years. Previous investigators have highlighted the unique features of RDH12-associated retinal degeneration compared to other forms of LCA, including the early appearance of macular atrophy and peripheral RPE atrophy in early childhood, followed by bone spicule pigment in late childhood or early adulthood (Perrault et al 2004;Schuster et al 2007;Sodi et al 2010;Mackay et al 2011;Chacon-Camacho et al 2013;Zou et al 2018). This is contrast to other forms of LCA that demonstrate normal fundus appearance despite marked retinal dysfunction.…”

“…A literature search was performed in PubMed with terms "RDH12" or "Retinol dehydrogenase 12," and publications were included with phenotypic data on human subjects with genetically confirmed RDH12-associated retinal degeneration. Eighteen publications were included and reported phenotypic data on 222 subjects (Janecke et al 2004;Perrault et al 2004;Thompson et al 2005;Jacobson et al 2007;Schuster et al 2007;Sun et al 2007;Benayoun et al 2009;Valverde et al 2009;Sodi et al 2010;Walia et al 2010;Mackay et al 2011;Chacon-Camacho et al 2013;Beryozkin et al 2014;Kuniyoshi et al 2014;Sanchez-Alcudia et al 2014;Yucel-Yilmaz et al 2014;Gong et al 2015;Zou et al 2018). Phenotypic data was published for 134 individual subjects, with the remaining 88 subjects included in aggregate data reporting.…”

Phenotype-genotype correlation with Sanger sequencing identified retinol dehydrogenase 12 (RDH12) compound heterozygous variants in a Chinese family with Leber congenital amaurosis

“…Although phenotypic variability could be found in the complete ophthalmic examinations of LCA patients, some specific clinical features could provide significant prognostic information for determining which gene may be responsible and thereby significantly reducing the involved cost. LCA 13, the characteristic phenotype associated with RDH12 mutations, exhibits severe and homogeneous clinical features characterized by onset of symptoms in early childhood and progression to legal blindness in early adulthood due to significant loss of the function of both rods and cones (Janecke et al, 2004), with fundi showing marked pigmentary retinopathy with bone spicules in the peripheral retina and pronounced maculopathy (Jacobson et al, 2007;Valverde et al, 2009;Sodi et al, 2010;Kuniyoshi et al, 2014). Nyctalopia is the predominant symptom of LCA 13.…”