Confirmation of the Role of DHX38 in the Etiology of Early-Onset Retinitis Pigmentosa.

TitleConfirmation of the Role of DHX38 in the Etiology of Early-Onset Retinitis Pigmentosa.
Publication TypeJournal Article
Year of Publication2018
AuthorsLatif, Z, Chakchouk, I, Schrauwen, I, Lee, K, Santos-Cortez, RLyn P, Abbe, I, Acharya, A, Jarral, A, Ali, I, Ullah, E, Khan, MNasim, Ali, G, Tahir, THussain, Bamshad, MJ, Nickerson, DA, Ahmad, W, Ansar, M, Leal, SM
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics (UWCMG) Study Group
JournalInvest Ophthalmol Vis Sci
Date Published2018 09 04
KeywordsAdolescent, Adult, Cataract, Computational Biology, DEAD-box RNA Helicases, Female, Genes, Recessive, Genetic Association Studies, Genetic Linkage, Humans, Male, Mutation, Missense, Nucleotide Mapping, Ophthalmoscopy, Pedigree, Retinitis Pigmentosa, RNA Splicing Factors, Sequence Analysis, DNA, Whole Exome Sequencing, Young Adult

Purpose: Retinitis pigmentosa (RP) is a genetically heterogeneous trait with autosomal-recessive (ar) inheritance underlying 50% of genetic disease cases. Sixty-one arRP genes have been identified, and recently, DHX38 has been reported as a potential candidate gene for arRP with only a single family reported with a variant of unknown significance. We identified a missense variant in DHX38 that co-segregates with the arRP phenotype in two Pakistani families confirming the involvement of DHX38 in the etiology of early-onset RP.

Methods: Exome sequencing was performed using two DNA samples from affected members of Pakistani families (MA88 and MA157) with early onset arRP. Sanger sequencing of DNA samples from all family members confirmed the segregation of candidate variant within both families.

Results: A novel missense DHX38 variant c.971G>A; p.(Arg324Gln) was identified which segregates with the arRP phenotype and yielded a logarithm of the odds (LOD) score of 5.0 and 4.3 for families MA88 and MA157, respectively. This variant is predicted to be conserved and deleterious by several bioinformatics tools.

Conclusions: We identified a second deleterious DHX38 variant that segregates with arRP in two families, providing additional evidence that DHX38 is involved in RP etiology. DHX38 encodes for pre-mRNA splicing factor PRP16, which is important in catalyzing pre-mRNA splicing.

Alternate JournalInvest. Ophthalmol. Vis. Sci.
PubMed ID30208423
PubMed Central IDPMC6133250
Grant ListU54 HG006493 / HG / NHGRI NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States