Expanding the phenotypic spectrum in RDH12-associated retinal disease.

TitleExpanding the phenotypic spectrum in RDH12-associated retinal disease.
Publication TypeJournal Article
Year of Publication2020
AuthorsScott, HA, Place, EM, Ferenchak, K, Zampaglione, E, Wagner, NE, Chao, KR, DiTroia, SP, Navarro-Gomez, D, Mukai, S, Huckfeldt, RM, Pierce, EA, Bujakowska, KM
JournalCold Spring Harb Mol Case Stud
Date Published2020 02
KeywordsAdolescent, Adult, Alcohol Oxidoreductases, Alleles, Amino Acid Substitution, Child, Child, Preschool, Female, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Humans, Male, Mutation, Optical Imaging, Pedigree, Phenotype, Retinal Diseases, Tomography, Optical Coherence, Whole Exome Sequencing, Young Adult

Retinol dehydrogenase 12, RDH12, plays a pivotal role in the visual cycle to ensure the maintenance of normal vision. Alterations in activity of this protein result in photoreceptor death and decreased vision beginning at an early age and progressing to substantial vision loss later in life. Here we describe 11 patients with retinal degeneration that underwent next-generation sequencing (NGS) with a targeted panel of all currently known inherited retinal degeneration (IRD) genes and whole-exome sequencing to identify the genetic causality of their retinal disease. These patients display a range of phenotypic severity prompting clinical diagnoses of macular dystrophy, cone-rod dystrophy, retinitis pigmentosa, and early-onset severe retinal dystrophy all attributed to biallelic recessive mutations in We report 15 causal alleles and expand the repertoire of known mutations with four novel variants: c.215A > G (p.Asp72Gly); c.362T > C (p.Ile121Thr); c.440A > C (p.Asn147Thr); and c.697G > A (p.Val233Ille). The broad phenotypic spectrum observed with biallelic mutations has been observed in other genetic forms of IRDs, but the diversity is particularly notable here given the prior association of primarily with severe early-onset disease. This breadth emphasizes the importance of broad genetic testing for inherited retinal disorders and extends the pool of individuals who may benefit from imminent gene-targeted therapies.

Alternate JournalCold Spring Harb Mol Case Stud
PubMed ID32014858
PubMed Central IDPMC6996522
Grant ListR01 EY012910 / EY / NEI NIH HHS / United States
R01 EY026904 / EY / NEI NIH HHS / United States
R01 HG009141 / HG / NHGRI NIH HHS / United States
UM1 HG008900 / HG / NHGRI NIH HHS / United States
P30 EY014104 / EY / NEI NIH HHS / United States