PDF(Pubmed)
Abstract：
CNGB1 gene mutations are a well-known cause of autosomal recessive retinitis pigmentosa (RP), which was recently associated with olfactory dysfunction. The purpose of this study was to report the molecular spectrum and the ocular and olfactory phenotypes of a multiethnic cohort with CNGB1-associated RP. A cross-sectional case series was conducted at two ophthalmic genetics referral centers. Consecutive patients with molecularly confirmed CNGB1-related RP were included. All patients underwent a complete ophthalmological examination complemented by psychophysical olfactory evaluation. Fifteen patients (10 families: 8 Portuguese, 1 French, and 1 Turkish), mean aged 57.13 ± 15.37 years old (yo), were enrolled. Seven disease-causing variants were identified, two of which are reported for the first time: c.2565_2566del and c.2285G > T. Although 11/15 patients reported onset of nyctalopia before age 10, diagnosis was only established after 30 yo in 9/15. Despite widespread retinal degeneration being present in 14/15 probands, a relatively preserved visual acuity was observed throughout follow-up. Olfactory function was preserved in only 4/15 patients, all of whom carried at least one missense variant. Our study supports previous reports of an autosomal recessive RP-olfactory dysfunction syndrome in association with certain disease-causing variants in the CNGB1 gene and expands the mutational spectrum of CNGB1-related disease by reporting two novel variants.
摘要：
CNGB1基因突变是众所周知的常染色体隐性遗传性视网膜色素变性（RP）的原因，最近与嗅觉功能障碍有关。这项研究的目的是报告与CNGB1相关RP的多种族队列的分子光谱以及眼部和嗅觉表型。在两个眼科遗传学转诊中心进行了横断面病例系列。连续纳入分子证实为CNGB1相关RP的患者。所有患者均接受了完整的眼科检查，并进行了心理物理嗅觉评估。15名患者（10个家庭：8个葡萄牙语，1法语,和1个土耳其语），平均年龄57.13±15.37岁(yo)，已注册。确定了七种致病变异，其中两个是首次报告的：c.2565_2566del和c.2285G>T。尽管11/15患者在10岁之前报告了夜盲症的发作，但仅在9/15的30岁后才确定诊断。尽管14/15先证者存在广泛的视网膜变性，在整个随访期间观察到相对保持的视力.只有4/15的患者保留了嗅觉功能，所有这些人都携带至少一个错觉变体。我们的研究支持了与CNGB1基因中某些致病变异相关的常染色体隐性遗传RP-嗅觉功能障碍综合征的先前报道，并通过报道两个新的变异扩大了CNGB1相关疾病的突变谱。
