Abstract：
Axial spondylometaphyseal dysplasia(axial SMD) is associated with early-onset retinal dystrophy and various skeletal dysplasias of varying severity. NEK1 is the causative gene for short rib polydactyly syndrome and axial SMD. Here, we report a case of siblings with juvenile retinitis pigmentosa (RP) and NEK1 variants not associated with systemic disorders.
The patients were a 7-year-old-girl and a 9-year-old boy with RP, who were followed for 9 years. Whole exome sequencing (WES) was performed on the siblings and their parents, who were not consanguineous.
The corrected visual acuity of the girl and the boy at first visit was binocular 20/63 and 20/100 OD and 20/63 OS, respectively. The siblings had narrowing of retinal blood vessels and retinal pigment epithelium atrophy in the fundus and showed an extinguished pattern in electroretinogram. On optical coherence tomography, there was a mottled ellipsoid band with progressive loss in the outer macular, the edges of which corresponded to the ring of hyperautofluorescence on fundus autofluorescence imaging. The siblings showed progressive visual field constriction. Radiological examination did not reveal any skeletal abnormalities. We identified two rare heterozygous NEK1 variants in the patients: c.240 G>A; p.(M80I) and c.634_639dup;p.(V212_L213dup). Heterozygous variants were recognized in the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic.
This is the first report of RP patients with NEK1 variants not associated with skeletal abnormalities.
The patients were a 7-year-old-girl and a 9-year-old boy with RP, who were followed for 9 years. Whole exome sequencing (WES) was performed on the siblings and their parents, who were not consanguineous.
The corrected visual acuity of the girl and the boy at first visit was binocular 20/63 and 20/100 OD and 20/63 OS, respectively. The siblings had narrowing of retinal blood vessels and retinal pigment epithelium atrophy in the fundus and showed an extinguished pattern in electroretinogram. On optical coherence tomography, there was a mottled ellipsoid band with progressive loss in the outer macular, the edges of which corresponded to the ring of hyperautofluorescence on fundus autofluorescence imaging. The siblings showed progressive visual field constriction. Radiological examination did not reveal any skeletal abnormalities. We identified two rare heterozygous NEK1 variants in the patients: c.240 G>A; p.(M80I) and c.634_639dup;p.(V212_L213dup). Heterozygous variants were recognized in the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic.
This is the first report of RP patients with NEK1 variants not associated with skeletal abnormalities.
摘要：
未经证实：轴性脊椎部骨干发育不良(轴性SMD)与早发性视网膜营养不良和各种不同严重程度的骨骼发育不良相关。NEK1是短肋骨多指综合征和轴性SMD的致病基因。这里,我们报道了1例青少年视网膜色素变性(RP)和NEK1变异与全身性疾病无关的兄弟姐妹。
未经证实：患者是一名7岁女孩和一名9岁男孩，患有RP，他们被跟踪了9年。对兄弟姐妹及其父母进行全外显子组测序（WES），他们不是血缘关系。
未经证实：第一次就诊时女孩和男孩的矫正视力为双目20/63和20/100OD和20/63OS，分别。兄弟姐妹的眼底视网膜血管变窄和视网膜色素上皮萎缩，并在视网膜电图中显示出熄灭的模式。在光学相干层析成像上，外黄斑有一条斑驳的椭球带，逐渐消失，其边缘对应于眼底自发荧光成像上的超自发荧光环。兄弟姐妹表现出渐进的视野收缩。放射学检查未发现任何骨骼异常。我们在患者中鉴定出两种罕见的杂合NEK1变体：c.240G>A；p。（M80I）和c.634_639dup；p。（V212_L213dup）。在父亲和母亲中识别杂合变体，分别。根据美国医学遗传学和基因组学学院的指导方针，两种变异均被分类为可能致病.
UNASSIGNED：这是首例NEK1变异与骨骼异常无关的RP患者的报告。
未经证实：患者是一名7岁女孩和一名9岁男孩，患有RP，他们被跟踪了9年。对兄弟姐妹及其父母进行全外显子组测序（WES），他们不是血缘关系。
未经证实：第一次就诊时女孩和男孩的矫正视力为双目20/63和20/100OD和20/63OS，分别。兄弟姐妹的眼底视网膜血管变窄和视网膜色素上皮萎缩，并在视网膜电图中显示出熄灭的模式。在光学相干层析成像上，外黄斑有一条斑驳的椭球带，逐渐消失，其边缘对应于眼底自发荧光成像上的超自发荧光环。兄弟姐妹表现出渐进的视野收缩。放射学检查未发现任何骨骼异常。我们在患者中鉴定出两种罕见的杂合NEK1变体：c.240G>A；p。（M80I）和c.634_639dup；p。（V212_L213dup）。在父亲和母亲中识别杂合变体，分别。根据美国医学遗传学和基因组学学院的指导方针，两种变异均被分类为可能致病.
UNASSIGNED：这是首例NEK1变异与骨骼异常无关的RP患者的报告。
