Ruben Jauregui1, Karen Sophia Park2, Akemi J Tanaka3, Ahra Cho4, Maarjaliis Paavo5, Jana Zernant5, Jasmine H Francis6, Rando Allikmets7, Janet R Sparrow8, Stephen H Tsang9. 1. Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, New York, New York, USA; Weill Cornell Medical College, New York, New York, USA. 2. Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, New York, New York, USA. 3. Department of Pathology & Cell Biology, Columbia University Medical Center, New York, New York, USA. 4. Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, New York, New York, USA; Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York, USA. 5. Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA. 6. Memorial Sloan Kettering Cancer Center, New York, New York, USA. 7. Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA; Department of Pathology & Cell Biology, Columbia University Medical Center, New York, New York, USA. 8. Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA; Department of Pathology & Cell Biology, Columbia University Medical Center, New York, New York, USA; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, New York, New York, USA. 9. Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA; Department of Pathology & Cell Biology, Columbia University Medical Center, New York, New York, USA; Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, New York, New York, USA. Electronic address: sht2@cumc.columbia.edu.
Abstract
PURPOSE: To characterize and bring awareness to the disease spectrum of female choroideremia patients, as severity can vary from mild to severe disease, comparable to that observed in male patients. DESIGN: Retrospective cohort study. METHODS: Twelve female carriers of disease-causing variants in the CHM gene confirmed by molecular genetic sequencing were characterized clinically and imaged with short-wave fundus autofluorescence (SW-FAF), spectral-domain optical coherence tomography (OCT), and color fundus imaging. RESULTS: Twelve unrelated female patients with a clinical and genetic diagnosis of choroideremia carriers were included in this study. Disease severity among these phenotypes ranged from mild to severe, resembling the typical presentation of choroideremia in male patients. Mild disease presented with retinal pigment epithelium mottling, a patchy pattern of hypoautofluorescent speckles on SW-FAF, and intact retinal layers on spectral-domain OCT. Severe disease presented with widespread chorioretinal atrophy as shown by SW-FAF and spectral-domain OCT. Each of the identified genetic variants in CHM was predicted to be disease-causing according to in silico prediction software. Disease progression analysis of 4 patients with follow-up showed a decline in visual acuity for 2 patients, with progression observed on spectral-domain OCT in 1 of the patients. No significant disease progression on SW-FAF was observed for any of the patients. CONCLUSIONS: Female carriers of choroideremia can present with a wide range of clinical phenotypes and disease severity, from mild to severe disease, similar to male subjects. Symptomatic female subjects should be considered for current and upcoming gene replacement therapy clinical trials.
PURPOSE: To characterize and bring awareness to the disease spectrum of female choroideremiapatients, as severity can vary from mild to severe disease, comparable to that observed in male patients. DESIGN: Retrospective cohort study. METHODS: Twelve female carriers of disease-causing variants in the CHM gene confirmed by molecular genetic sequencing were characterized clinically and imaged with short-wave fundus autofluorescence (SW-FAF), spectral-domain optical coherence tomography (OCT), and color fundus imaging. RESULTS: Twelve unrelated female patients with a clinical and genetic diagnosis of choroideremia carriers were included in this study. Disease severity among these phenotypes ranged from mild to severe, resembling the typical presentation of choroideremia in male patients. Mild disease presented with retinal pigment epithelium mottling, a patchy pattern of hypoautofluorescent speckles on SW-FAF, and intact retinal layers on spectral-domain OCT. Severe disease presented with widespread chorioretinal atrophy as shown by SW-FAF and spectral-domain OCT. Each of the identified genetic variants in CHM was predicted to be disease-causing according to in silico prediction software. Disease progression analysis of 4 patients with follow-up showed a decline in visual acuity for 2 patients, with progression observed on spectral-domain OCT in 1 of the patients. No significant disease progression on SW-FAF was observed for any of the patients. CONCLUSIONS: Female carriers of choroideremia can present with a wide range of clinical phenotypes and disease severity, from mild to severe disease, similar to male subjects. Symptomatic female subjects should be considered for current and upcoming gene replacement therapy clinical trials.
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