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.
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。