McLaren Terri L, De Roach John N, Thompson Jennifer A, Chen Fred K, Mackey David A, Hoffmann Ling, Urwin Isabella R, Lamey Tina M
Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia Australia.
Centre for Ophthalmology and Visual Science, The University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia Australia.
Hum Genome Var. 2020 Oct 23;7:35. doi: 10.1038/s41439-020-00122-w. eCollection 2020.
Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in the gene. Several gene replacement clinical trials are in advanced stages. In this study, we report the molecular confirmation of choroideremia in 14 Australian families sourced from the Australian Inherited Retinal Disease Registry and DNA Bank. Sixteen males (14 symptomatic) and 18 females (4 symptomatic; 14 obligate carriers) were identified for analysis. Participants' DNA was analyzed for disease-causing variants by Sanger sequencing, TaqMan qPCR and targeted NGS. We report phenotypic and genotypic data for the 14 symptomatic males and four females manifesting disease symptoms. A pathogenic or likely pathogenic variant was detected in all families. Eight variants were previously reported, and five were novel. Two variants were identified. We previously reported the molecular confirmation of choroideremia in 11 Australian families. This study expands the genetically confirmed Australian cohort to 32 males and four affected carrier females.
无脉络膜症是一种由该基因的突变引起的X连锁性脉络膜视网膜营养不良。几项基因替代临床试验正处于后期阶段。在本研究中，我们报告了来自澳大利亚遗传性视网膜疾病登记处和DNA库的14个澳大利亚家庭中无脉络膜症的分子确诊情况。共确定了16名男性（14名有症状）和18名女性（4名有症状；14名肯定携带者）进行分析。通过桑格测序、TaqMan定量PCR和靶向二代测序对参与者的DNA进行致病变异分析。我们报告了14名有症状男性和4名表现出疾病症状的女性的表型和基因型数据。在所有家庭中均检测到一个致病或可能致病的变异。8个变异先前已有报道，5个为新发现的变异。确定了两个变异。我们之前报告了11个澳大利亚家庭中无脉络膜症的分子确诊情况。本研究将经基因确认的澳大利亚队列扩大到32名男性和4名患病携带者女性。
