Frequency and phenotypic characteristics of RPE65 mutations in the Chinese population
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Frequency and phenotypic characteristics of RPE65 mutations in the Chinese population. / Gao, Feng-Juan; Wang, Dan-Dan; Li, Jian-Kang; Hu, Fang-Yuan; Xu, Ping; Chen, Fang; Qi, Yu-He; Liu, Wei; Li, Wei; Zhang, Sheng-Hai; Chang, Qing; Xu, Ge-Zhi; Wu, Ji-Hong.
In: Orphanet Journal of Rare Diseases, Vol. 16, 174, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Frequency and phenotypic characteristics of RPE65 mutations in the Chinese population
AU - Gao, Feng-Juan
AU - Wang, Dan-Dan
AU - Li, Jian-Kang
AU - Hu, Fang-Yuan
AU - Xu, Ping
AU - Chen, Fang
AU - Qi, Yu-He
AU - Liu, Wei
AU - Li, Wei
AU - Zhang, Sheng-Hai
AU - Chang, Qing
AU - Xu, Ge-Zhi
AU - Wu, Ji-Hong
PY - 2021
Y1 - 2021
N2 - Background The retinoid isomerohydrolase RPE65 has received considerable attention worldwide since a successful clinical gene therapy was approved in 2017 as the first treatment for vision loss associated with RPE65-mediated inherited retinal disease. Identifying patients with RPE65 mutations is a prerequisite to assessing the patients' eligibility to receive RPE65-targeted gene therapies, and it is necessary to identify individuals who are most likely to benefit from gene therapies. This study aimed to investigate the RPE65 mutations frequency in the Chinese population and to determine the genetic and clinical characteristics of these patients. Results Only 20 patients with RPE65 mutations were identified, and RPE65 mutations were determined to be the 14th most common among all patients with genetic diagnoses. Ten novel variants and two hotspots associated with FAP were identified. A literature review revealed that a total of 57 patients of Chinese origin were identified with pathogenic mutations in the RPE65 gene. The mean best Snellen corrected visual acuity was worse (mean 1.3 +/- 1.3 LogMAR) in patients older than 20 years old than in those younger than 15 years old (0.68 +/- 0.92 LogMAR). Bone spicule-like pigment deposits (BSLPs) were observed in six patients; they were older than those without BSLP and those with white-yellow dots. Genotype-phenotype analysis revealed that truncating variants seem to lead to a more severe clinical presentation, while best corrected visual acuity testing and fundus changes did not correlate with specific RPE65 variants or mutation types. Conclusions This study provides a detailed clinical-genetic assessment of patients with RPE65 mutations of Chinese origin. These results may help to elucidate RPE65 mutations in the Chinese population and may facilitate genetic counseling and the implementation of gene therapy in China.
AB - Background The retinoid isomerohydrolase RPE65 has received considerable attention worldwide since a successful clinical gene therapy was approved in 2017 as the first treatment for vision loss associated with RPE65-mediated inherited retinal disease. Identifying patients with RPE65 mutations is a prerequisite to assessing the patients' eligibility to receive RPE65-targeted gene therapies, and it is necessary to identify individuals who are most likely to benefit from gene therapies. This study aimed to investigate the RPE65 mutations frequency in the Chinese population and to determine the genetic and clinical characteristics of these patients. Results Only 20 patients with RPE65 mutations were identified, and RPE65 mutations were determined to be the 14th most common among all patients with genetic diagnoses. Ten novel variants and two hotspots associated with FAP were identified. A literature review revealed that a total of 57 patients of Chinese origin were identified with pathogenic mutations in the RPE65 gene. The mean best Snellen corrected visual acuity was worse (mean 1.3 +/- 1.3 LogMAR) in patients older than 20 years old than in those younger than 15 years old (0.68 +/- 0.92 LogMAR). Bone spicule-like pigment deposits (BSLPs) were observed in six patients; they were older than those without BSLP and those with white-yellow dots. Genotype-phenotype analysis revealed that truncating variants seem to lead to a more severe clinical presentation, while best corrected visual acuity testing and fundus changes did not correlate with specific RPE65 variants or mutation types. Conclusions This study provides a detailed clinical-genetic assessment of patients with RPE65 mutations of Chinese origin. These results may help to elucidate RPE65 mutations in the Chinese population and may facilitate genetic counseling and the implementation of gene therapy in China.
KW - Inherited retinal dystrophy
KW - RPE65 gene mutations
KW - Next-generation sequencing
KW - Chinese population
KW - Genotype–
KW - phenotype correlations
U2 - 10.1186/s13023-021-01807-3
DO - 10.1186/s13023-021-01807-3
M3 - Journal article
C2 - 33952291
VL - 16
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
SN - 1750-1172
M1 - 174
ER -
ID: 262899587