TY - JOUR
T1 - Biallelic null variants in C19orf44 cause a unique late-onset retinal dystrophy phenotype characterized by patchy perifoveal chorioretinal atrophy
AU - Ehrenberg, Miriam
AU - Avraham, Maayan
AU - Asodu, Sandeep Sarma
AU - Moye, Abigail R.
AU - Sangermano, Riccardo
AU - Rizel, Leah
AU - Ali-Nasser, Tahleel
AU - Sher, Ifat
AU - Gurwitz, David
AU - Chao, Katherine R.
AU - Rivera, Antonio
AU - Webster, Andrew R.
AU - Rivolta, Carlo
AU - Newman, Hadas
AU - Pras, Eran
AU - Rotenstreich, Ygal
AU - Banin, Eyal
AU - Pierce, Eric A.
AU - Zur, Dinah
AU - Arno, Gavin
AU - Bujakowska, Kinga M.
AU - Lin, Siying
AU - Sharon, Dror
AU - Ben-Yosef, Tamar
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/6
Y1 - 2025/6
N2 - Purpose: To identify the genetic cause for disease in individuals affected with inherited retinal disease and to characterize their retinal phenotype and the properties of the underlying gene. Methods: Participants underwent a comprehensive ophthalmological evaluation, including best-corrected visual acuity, visual field testing, fundus autofluorescence, optical coherence tomography, and electroretinography. Genetic analyses included exome, genome, and Sanger sequencing. Gene expression pattern was analyzed by reverse transcription-polymerase chain reaction. Localization of the encoded protein in cells and in the human retina was examined by immunofluorescence staining. Results: Four different pathogenic variants in C19orf44 were identified in 15 biallelic individuals from 11 unrelated families. The most common variant was c.549_550del p.(Ser185ProfsTer2). Most individuals were affected with a unique clinical phenotype characterized by late-onset patchy perifoveal chorioretinal atrophy and electroretinographic features of rod-cone degeneration. C19orf44 is expressed in various human tissues, including the retina, where it was found in the outer nuclear layer and in the outer plexiform layer. In cultured cells (hTERT RPE-1 and HeLa) and in human primary fibroblasts, C19orf44 is found in the nucleus, and it is downregulated during mitosis. Conclusion: Based on our results, C19orf44 is crucial for normal human retinal function, and pathogenic variants in this gene are associated with autosomal recessive inherited retinal disease.
AB - Purpose: To identify the genetic cause for disease in individuals affected with inherited retinal disease and to characterize their retinal phenotype and the properties of the underlying gene. Methods: Participants underwent a comprehensive ophthalmological evaluation, including best-corrected visual acuity, visual field testing, fundus autofluorescence, optical coherence tomography, and electroretinography. Genetic analyses included exome, genome, and Sanger sequencing. Gene expression pattern was analyzed by reverse transcription-polymerase chain reaction. Localization of the encoded protein in cells and in the human retina was examined by immunofluorescence staining. Results: Four different pathogenic variants in C19orf44 were identified in 15 biallelic individuals from 11 unrelated families. The most common variant was c.549_550del p.(Ser185ProfsTer2). Most individuals were affected with a unique clinical phenotype characterized by late-onset patchy perifoveal chorioretinal atrophy and electroretinographic features of rod-cone degeneration. C19orf44 is expressed in various human tissues, including the retina, where it was found in the outer nuclear layer and in the outer plexiform layer. In cultured cells (hTERT RPE-1 and HeLa) and in human primary fibroblasts, C19orf44 is found in the nucleus, and it is downregulated during mitosis. Conclusion: Based on our results, C19orf44 is crucial for normal human retinal function, and pathogenic variants in this gene are associated with autosomal recessive inherited retinal disease.
KW - C19orf44
KW - Chorioretinal atrophy
KW - Inherited retinal disease
KW - Retina
UR - http://www.scopus.com/inward/record.url?scp=105004908207&partnerID=8YFLogxK
U2 - 10.1016/j.gim.2025.101401
DO - 10.1016/j.gim.2025.101401
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C2 - 40079362
AN - SCOPUS:105004908207
SN - 1098-3600
VL - 27
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 6
M1 - 101401
ER -