Identification of novel deletions as the underlying cause of retinal degeneration in two pedigrees

Kari Branham, Aditya A. Guru, Igor Kozak, Pooja Biswas, Mohammad Othman, Kameron Kishaba, Hassan Mansoor, Sheikh Riazuddin, John R. Heckenlively, S. Amer Riazuddin, J. Fielding Hejtmancik, Paul A. Sieving, Radha Ayyagari

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations


Retinal dystrophies are a phenotypically and genetically complex group of conditions. Because of this complexity, it can be challenging in many families to determine the inheritance based on pedigree analysis alone. Clinical examinations were performed and blood samples were collected from a North American (M1186) and a consanguineous Pakistani (PKRD168) pedigree affected with two different retinal dystrophies (RD). Based on the structure of the pedigrees, inheritance patterns in the families were difficult to determine. In one family, linkage analysis was performed with markers on X-chromosome. In the second family, whole-exome sequencing (WES) was performed. Subsequent Sanger sequencing of genes of interest was performed. Linkage and haplotype analysis localized the disease interval to a 70 Mb region on the X chromosome that encompassed RP2 and RPGR in M1186. The disease haplotype segregated with RD in all individuals except for an unaffected man (IV:3) and his affected son (V:1) in this pedigree. Subsequent analysis identified a novel RPGR mutation (p. Lys857Glu fs221X) in all affected members of M1186 except V:1. This information suggests that there is an unidentified second cause of retinitis pigmentosa (RP) within the family. A novel two-base-pair deletion (p. Tyr565Ter fsX) in CHM (choroideremia) was found to segregate with RD in PKRD168. This paper highlights the challenges of interpreting family history in families with RD and reports on the identification of novel mutations in two RD families.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Number of pages8
StatePublished - 2018

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • Choroideremia
  • Deletions
  • Exome sequencing
  • Linkage analysis
  • RPGR
  • XLRP

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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