Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the loss of both upper and lower motor neurons. Approximately 10% of patients with ALS have a family history of the disease, and 22 genes have already been reported to be implicated in ALS.1 In previous reports, some of the genes implicated in ALS were associated with visual dysfunctions; however, no cases have yet reported patients presenting clinically both ALS and ocular abnormalities.1 Recently, a large case-controlled genome-wide association study (GWAS) of ALS revealed cilia and flagella-associated protein 410 ( CFAP410 ), previously called as C21orf2 .2 CFAP410 is causative for axial spondylometaphyseal dysplasia (SMDAX), which presents with retinitis pigmentosa (RP), and retinal dystrophy (RD) with or without macular staphyloma.3 However, no hereditary ALS cases have yet reported CFAP410 variants. In this letter, we provide the first description of siblings with RP and ALS with the causative CFAP410 mutation. They showed RP until their fourth decade and muscle weakness of the extremities started more than 10 years after the diagnosis of RP. The pedigree chart of the affected family is presented in figure 1A. Their parents (I-1 and I-2) were consanguineous and neurologically healthy. Figure 1 (A) Pedigree chart of the affected family. Shaded boxes represent affected members. Symbols having diagonal lines represent deceased individuals. Unaffected family members exhibited no abnormalities during their medical examinations. (B) Sanger sequencing revealed that the patients had exon 4 of a CFAP410 homozygous variant (c.319T>C, p.Y107H) and that the non-affected sibling had a heterozygous variant of CFAP410 . (C) Heterozygous CFAP410 variants of amyotrophic lateral sclerosis (ALS) (black) were previously detected except for exon 2. On the other hand, causative …

中文翻译：

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由纯合纤毛和鞭毛相关蛋白410突变引起的家族性ALS之前的色素性视网膜炎。

肌萎缩性侧索硬化症（ALS）是一种致命的神经退行性疾病，由上，下运动神经元的缺失引起。约有10％的ALS患者有该病的家族病史，并且已经报道22个基因与ALS有关。1在以前的报道中，与ALS有关的一些基因与视觉功能障碍有关；然而，目前尚无病例报告临床上同时表现为ALS和眼部异常的患者。1最近，一项大型的病例对照全基因组关联研究（GWAS）揭示了纤毛和鞭毛相关蛋白410（CFAP410），以前称为C21orf2 .2 CFAP410是引起轴突性脊柱后凸发育不良（SMDAX）的原因，其表现为色素性视网膜炎（RP）和伴或不伴黄斑性葡萄球瘤的视网膜营养不良（RD）。3然而，尚无遗传性ALS病例报告CFAP410变体。在这封信中，我们提供了具有致病性CFAP410突变的RP和ALS兄弟姐妹的第一个描述。他们一直表现为RP，直到他们的第四个十年，四肢肌肉无力开始于RP的诊断开始超过10年。受影响家庭的血统书如图1A所示。他们的父母（I-1和I-2）近亲且神经系统健康。图1（A）受影响家庭的谱系图。阴影框表示受影响的成员。具有对角线的符号表示已故的个人。未受影响的家庭成员在体检过程中未表现出异常。（B）Sanger测序显示患者具有CFAP410纯合变异体的外显子4（c.319T> C，p。Y107H），并且未受影响的兄弟姐妹具有CFAP410的杂合变异体。（C）除外显子2外，先前检测到了肌萎缩性侧索硬化症（ALS）（黑色）的杂合CFAP410变体。