PDF(Pubmed)
Abstract：
BACKGROUND: We describe the case of a 47-year-old man referred to a retinal clinic and diagnosed with late-onset retinitis pigmentosa. Surprisingly, genetic testing revealed compound heterozygous pathogenic variants in GNPTG, leading to the diagnosis of the autosomal recessive lysosomal storage disorder mucolipidosis type III gamma. Mucolipidosis type III gamma is typically diagnosed during childhood due to symptoms relating to skeletal dysplasia. Retinal dystrophy is not a common phenotypic feature.
METHODS: Ophthalmologic examination was consistent with a mild form of retinitis pigmentosa and included fundus photography, measurement of best-corrected visual acuity, optical coherence tomography, electroretinogram and visual field testing. Extraocular findings included joint restriction and pains from an early age leading to bilateral hip replacement by age 30, aortic insufficiency, and hypertension. Genetic analysis was performed by whole genome sequencing filtered for a gene panel of 325 genes associated with retinal disease. Two compound heterozygous pathogenic variants were identified in GNPTG, c.347_349del and c.607dup. The diagnosis of mucolipidosis type III gamma was confirmed biochemically by measurement of increased activities of specific lysosomal enzymes in plasma.
CONCLUSIONS: To our knowledge this is the first description of retinitis pigmentosa caused by compound heterozygous variants in GNPTG, providing further indications that late-onset retinal dystrophy is part of the phenotypic spectrum of mucolipidosis type III gamma.
METHODS: Ophthalmologic examination was consistent with a mild form of retinitis pigmentosa and included fundus photography, measurement of best-corrected visual acuity, optical coherence tomography, electroretinogram and visual field testing. Extraocular findings included joint restriction and pains from an early age leading to bilateral hip replacement by age 30, aortic insufficiency, and hypertension. Genetic analysis was performed by whole genome sequencing filtered for a gene panel of 325 genes associated with retinal disease. Two compound heterozygous pathogenic variants were identified in GNPTG, c.347_349del and c.607dup. The diagnosis of mucolipidosis type III gamma was confirmed biochemically by measurement of increased activities of specific lysosomal enzymes in plasma.
CONCLUSIONS: To our knowledge this is the first description of retinitis pigmentosa caused by compound heterozygous variants in GNPTG, providing further indications that late-onset retinal dystrophy is part of the phenotypic spectrum of mucolipidosis type III gamma.
摘要：
背景：我们描述了一名47岁的男性转诊到视网膜诊所并被诊断为迟发性色素性视网膜炎的情况。令人惊讶的是,基因检测显示GNPTG中的复合杂合致病变异，导致常染色体隐性遗传溶酶体贮积症III型γ型粘脂症的诊断。由于与骨骼发育不良有关的症状，通常在儿童期诊断为III型粘脂症。视网膜营养不良不是常见的表型特征。
方法：眼科检查与轻度色素性视网膜炎一致，包括眼底照相，最佳矫正视力的测量，光学相干层析成像，视网膜电图和视野测试。眼外发现包括关节受限和早期疼痛，导致30岁时双侧髋关节置换术，主动脉瓣关闭不全，和高血压。通过全基因组测序进行遗传分析,筛选与视网膜疾病相关的325个基因的基因组。在GNPTG中鉴定出两种复合杂合致病变异体，c.347_349del和c.607dup。通过测量血浆中特定溶酶体酶的活性增加，在生物化学上证实了III型粘液脂肪变性的诊断。
结论：据我们所知，这是由GNPTG中的复合杂合变体引起的视网膜色素变性的第一个描述，提供了进一步的迹象，表明迟发性视网膜营养不良是III型γ-粘脂菌病表型谱的一部分。
方法：眼科检查与轻度色素性视网膜炎一致，包括眼底照相，最佳矫正视力的测量，光学相干层析成像，视网膜电图和视野测试。眼外发现包括关节受限和早期疼痛，导致30岁时双侧髋关节置换术，主动脉瓣关闭不全，和高血压。通过全基因组测序进行遗传分析,筛选与视网膜疾病相关的325个基因的基因组。在GNPTG中鉴定出两种复合杂合致病变异体，c.347_349del和c.607dup。通过测量血浆中特定溶酶体酶的活性增加，在生物化学上证实了III型粘液脂肪变性的诊断。
结论：据我们所知，这是由GNPTG中的复合杂合变体引起的视网膜色素变性的第一个描述，提供了进一步的迹象，表明迟发性视网膜营养不良是III型γ-粘脂菌病表型谱的一部分。
