Prenatal diagnosis of choroideremia

Abstract

With the mapping of the locus CHM for choroideremia and the subsequent cloning of the gene, reliable carrier and prenatal diagnosis has become a possibility. We discuss our experience with prenatal diagnosis of choroideremia, an X‐linked choroidoretinal dystrophy leading to blindness in otherwise healthy males. In the period 1987–1995, five prenatal diagnoses have been performed by either indirect linkage analysis or by direct detection of the disease‐causing mutation, reflecting the impact of molecular biology in clinical genetic practice.

Understanding the impact of genetic testing for inherited retinal dystrophy

“…15 A strong motivating factor to seek genetic testing for RD has been reported to be the opportunity to access novel therapies 16 but, while such treatments remain unavailable for the vast majority of inherited retinal disorders, testing benefits are likely to centre on improving diagnosis, understanding of inheritance pattern and prognosis. 17 RP patients and at-risk family members have also reported interest in prenatal testing 15,18,19 and case studies describe use of pre-natal diagnosis 20 and pre-implantation genetic diagnosis. 21 Evaluation of the benefits of genetic testing for RD is complex as the measurement of clinical outcomes, in the absence of clinical interventions, remains ill-defined.…”

Choroideremia in a woman with ectodermal dysplasia and complex translocations involving chromosomes X, 1, and 3

“…The classic symptoms of impaired dark adaptation, signs of diffuse chorioretinal degeneration, peripheral field loss, a pattern of rod-cone degeneration followed by a flat ERG, and X-linked family history is considered diagnostic 9. Deoxyribonucleic acid (DNA) and immunoblot analysis are available for diagnostic confirmation, carrier testing, and/or preimplantation or prenatal diagnosis 10. DNA analysis can be done by targeted mutation analysis, sequence analysis, or duplication/deletion analysis 11–14…”

Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art

“…Choroideremia is caused by mutations in the CHM gene, which encodes component A of Rab geranylgeranyl-transferase, referred to as Rab escort protein 1 (REP1), a key mediator of posttranslational lipidation (prenylation) and subcellular localization of a family of intracellular protein trafficking regulators, known as the Rab GTPases (211). The CHM gene is ubiquitously expressed, but in most tissues, including adrenal gland, brain, and thyroid, the homolog REP2 protein partially counterbalances REP1 deficiency.…”