The impact of genetic testing in retinitis pigmentosa on reproductive medicine
Year: 2025
Type: article
Abstract: Dear Editor, Genetic testing in patients with retinitis pigmentosa (RP) is particularly important for individuals in their youth and reproductive age due to its several advantages, including prognosis determination and risk assessment for offspring. In many instances, genetic mutations reveal unexpected systemic associations, expanding our understanding of the disease beyond the ocular manifestations. Additionally, identifying genetic mutations in RP can occasionally have implications for reproductive medicine. We report the case of a 28-year-old female diagnosed with RP who was referred by a gynecologist for fundus evaluation and genetic testing to assess the risk of RP in her offspring. The patient and her husband, a known case of rheumatoid arthritis, were experiencing unexplained infertility and were undergoing artificial insemination. On fundus examination, her findings were consistent with RP; however, she exhibited sparse retinal pigmentation along with polydactyly. To determine the causative gene and inheritance pattern, we performed clinical exome sequencing to assess the potential risk for her offspring. While awaiting the genetic test results, she underwent two unsuccessful attempts at artificial insemination. Genetic testing identified a pathogenic mutation in the BBS12 gene—c. 1918del (p. Tyr640IlefsTer4)—a heterozygous single-base pair deletion in exon 2, leading to a frameshift and premature truncation of the protein four amino acids downstream of codon 640, classified as pathogenic based on ACMG guidelines. Based on these findings, we diagnosed her with Bardet–Biedl syndrome (BBS). RP associated with BBS is typically characterized by sparse retinal pigmentation, as observed in our patient.[1] She was not diabetic but exhibited features commonly associated with BBS, including obesity, short stature, coarse facial hair, and mild intellectual disability.[1] Ciliopathies, including BBS, are a group of disorders caused by dysfunction in primary non-motile cilia, which play a crucial role in sensory perception and various signaling pathways.[2] The dysfunction of these non-motile cilia explains the rod-cone degeneration, hearing impairment, and kidney dysfunction observed in BBS.[2] Furthermore, BBS is linked to hypogonadism in males and genital anomalies or polycystic ovaries in females. However, infertility in BBS patients is primarily attributed to impaired motility of spermatozoa and fallopian tubes.[2,3] The patient’s husband tested negative for the identified mutation. We communicated the genetic test results to the gynecologist, who, considering the implications of fallopian tube dysfunction in BBS, revised the couple’s reproductive plan to in vitro fertilization (IVF). This approach was successful, leading to conception. Although prenatal genetic testing and preimplantation genetic testing were discussed, they were not strongly emphasized, given the low recurrence risk of this autosomal recessive condition in their offspring. While genetic testing is often considered to have limited immediate therapeutic implications, this case underscores its clinical relevance in RP beyond disease prognosis. It highlights a significant application of genetic testing in guiding the selection of appropriate assisted reproductive techniques, ultimately facilitating successful conception in a patient with BBS. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.
Source: Indian Journal of Ophthalmology
Authors: Bansari Sorthiya, Puja Maitra
Institution: Aravind Eye Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4410816359