title: Genetic analysis and clinical phenotype of two Indian families with X-linked choroideremia.
abstract: OBJECTIVE
  This study aims to describe the phenotype and genotype of two Indian families affected with X-linked choroideremia (CHM).
  
  
  METHODS
  In these two families, the affected individuals and unaffected family members underwent a comprehensive ophthalmic examination including an optical coherence tomography (OCT) and electroretinogram. Blood samples were collected from the families for genetic analysis. Next generation sequencing (NGS) was done using a panel of 184 genes, which covered previously associated genes with retinal dystrophies. Sequencing data were analyzed for the CHM, RPGR, and RP2 genes that have been implicated in CHM and X-linked retinitis pigmentosa (XLRP), respectively. The identified variants were confirmed by Sanger sequencing in available individuals and unrelated controls.
  
  
  RESULTS
  In two unrelated male patients, NGS analysis revealed a previously reported 3'-splice site change c.820-1G>C in the CHM gene in the first family and hemizygous mutation c.653G>C (p.Ser218X) in the second family. The asymptomatic family members were carriers for these mutations. Spectral domain-OCT showed loss of outer retina, preservation of the inner retina, and choroidal thinning in the affected males and retinal pigment epithelial changes in the asymptomatic carriers. The identified mutations were not present in 100 controls of Indian origin. There were no potential mutations found in XLRP-associated (RPGR and RP2) genes.
  
  
  CONCLUSIONS
  This report describes the genotype and phenotype findings in patients with CHM from India. The identified genetic mutation leads to lack of Rab escort protein-1 (REP-1) or affects the production of a REP-1 protein that is likely to cause retinal abnormalities in patients.
authors.affiliation: Department of Vitreoretina, Narayana Nethralaya, Bengaluru, Karnataka, India.
authors.forename: Rajani
authors.initials: R
authors.lastname: Battu
authors.affiliation: Department of Molecular Signaling and Gene Therapy, Grow Research Laboratory, Narayana Nethralaya Foundation, Narayana Nethralaya, Bengaluru, Karnataka, India.
authors.forename: Nallathambi
authors.initials: N
authors.lastname: Jeyabalan
authors.affiliation: Department of Vitreoretina, Vittala International Institute of Ophthalmology, Bengaluru, Karnataka, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Murthy
authors.affiliation: Department of Genetics, Strand Life Sciences Pvt. Limited, Bengaluru, Karnataka, India.
authors.forename: Kavita S
authors.initials: KS
authors.lastname: Reddy
authors.affiliation: Department of Ophthalmology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jan Sag
authors.initials: JS
authors.lastname: Schouten
authors.affiliation: Department of Ophthalmology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Caroll A
authors.initials: CA
authors.lastname: Webers
mesh_terms: D000328:Adult; D015794:Choroideremia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D005136:Eye Proteins