2. Academic Validation
  3. Confirmation of the Role of DHX38 in the Etiology of Early-Onset Retinitis Pigmentosa

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

  • Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4552-4557. doi: 10.1167/iovs.18-23849.
Zahid Latif 1,  Imen Chakchouk 2,  Isabelle Schrauwen 2,  Kwanghyuk Lee 2,  Regie Lyn P Santos-Cortez 2,  Izoduwa Abbe 2,  Anushree Acharya 2,  Afeefa Jarral 3,  Imran Ali 4,  Ehsan Ullah 3,  Muhammad Nasim Khan 1,  Ghazanfar Ali 5,  Tufail Hussain Tahir 6,  Michael J Bamshad 7 8,  Deborah A Nickerson 7,  Wasim Ahmad 3,  Muhammad Ansar 3,  Suzanne M Leal 2,  University of Washington Center for Mendelian Genomics (UWCMG) Study Group
Affiliations

Affiliations

  • 1 Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan.
  • 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States.
  • 3 Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
  • 4 Department of Biotechnology, Mirpur University of Science and Technology (MUST), Mirpur, Pakistan.
  • 5 Department of Biotechnology, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan.
  • 6 Poonch Medical College, Rawalakot, Azad Jammu and Kashmir, Pakistan.
  • 7 Department of Genome Sciences, University of Washington, Seattle, Washington, United States.
  • 8 Department of Pediatrics, University of Washington, Seattle, Washington, United States.
PMID: 30208423 DOI: 10.1167/iovs.18-23849
Abstract

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.

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