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FB2026_01
,
released March 12, 2026
This report describes nystagmus 8, congenital, autosomal recessive. The human gene implicated in this disease is ROBO1, an axon guidance receptor that defines a novel subfamily of immunoglobulin superfamily proteins that is highly conserved from fruit flies to mammals. There are three orthologous genes in Drosophila, Dmel\robo1, Dmel\robo2, and Dmel\robo3, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Multiple UAS constructs of the human gene Hsap\ROBO1 have been introduced into flies, including wild-type ROBO1 and a gene carrying a mutational lesion implicated in this disease. See the 'Disease-Implicated Variants' table, below. Results in flies suggest that the characterized variant is a partial loss-of-function allele.
Amorphic and loss-of-function mutations of Dmel\robo1 are lethal; embryonic phenotypes exhibit axon pathfinding defects, with axons ectopically crossing the the ventral nerve cord midline.
A developmental and epileptic encephalopathy has also been associated with human ROBO1; see the Human Disease Model report 'developmental and epileptic encephalopathy (postulated), ROBO1-related' (FBhh0001475).
[updated Oct. 2024 by FlyBase; FBrf0222196]
Classic congenital or infantile nystagmus presents as conjugate, horizontal oscillations of the eyes, in primary or eccentric gaze, often with a preferred head turn or tilt. Other associated features may include mildly decreased visual acuity, strabismus, astigmatism, and occasionally head nodding. Eye movement recordings reveal that infantile nystagmus is predominantly a horizontal jerk waveform, with a diagnostic accelerating velocity slow phase. However, pendular and triangular waveforms may also be present. The nystagmus may rarely be vertical. As these patients often have normal visual acuity, it is presumed that the nystagmus represents a primary defect in the parts of the brain responsible for ocular motor control; thus the disorder has sometimes been termed 'congenital motor nystagmus' (Tarpey et al., 2006, pubmed:17013395; Shiels et al., 2007, pubmed:18087240) [from MIM:310700; 2023.06.21]
[NYSTAGMUS 8, CONGENITAL, AUTOSOMAL RECESSIVE; NYS8](https://omim.org/entry/257400)
[ROUNDABOUT GUIDANCE RECEPTOR 1; ROBO1](https://omim.org/entry/602430)
Three affected males in a single family exhibited bilateral horizontal nystagmus, with no other neurological or systemic abnormalties (Huang et al., 2022; pubmed:35348658; FBrf0254345).
Autosomal recessive congenital nystagmus-8 (NYS8) is characterized by the presence of bilateral horizontal nystagmus in the absence of other neurologic signs or symptoms. Brain imaging is normal (Huang et al., 2022; pubmed:35348658; FBrf0254345). [from MIM:257400; 2023.06.09]
This form of autosomal recessive congenital nystagmus is caused by homozygous mutation in the ROBO1 gene (Huang et al., 2022; pubmed:35348658; FBrf0254345).
Autosomal recessive congenital nystagmus-8 (NYS8) is caused by homozygous mutation in the ROBO1 gene on chromosome 3p12. [from MIM:257400; 2023.06.09]
The protein encoded by ROBO1 is a member of the immunoglobulin gene superfamily and encodes an integral membrane protein that functions in axon guidance and neuronal precursor cell migration. This receptor is activated by SLIT-family proteins, resulting in a repulsive effect on glioma cell guidance in the developing brain. [ Entrez:6091 ; 2022.09.22]
The ROBO1 gene encodes a receptor that is a member of the neural cell adhesion molecule family of receptors. ROBO1 acts as an axon guidance receptor that defines a novel subfamily of immunoglobulin superfamily proteins that is highly conserved from fruit flies to mammals (Kidd et al., 1998, pubmed:9458045). [from MIM:602430; 2023.06.09]
Many to many: multiple related genes in both species.
High-scoring ortholog of human ROBO2 moderate-scoring ortholog of human ROBO1 and ROBO3 (many Drosophila to many human).