A common NYX mutation in Flemish patients with X linked CSNB

Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium.
The British journal of ophthalmology (Impact Factor: 2.98). 08/2008; 93(5):692-6. DOI: 10.1136/bjo.2008.143727
Source: PubMed


The Schubert-Bornschein type of complete congenital stationary night blindness (CSNB) is a genetically heterogeneous retinal disorder. It is characterised by a non-progressive disease course, often associated with high myopia and nystagmus. So far, mutations in two genes, NYX (nyctalopin) and GRM6 (metabotropic glutamate receptor 6) have been associated with this form of CSNB. The purpose of this study was to identify the genetic defect in affected male patients from Flemish families with complete CSNB.
Probands with CSNB from three large Flemish families underwent ophthalmological examination. DNA was extracted from peripheral blood, and the coding region of NYX along with parts of the 5'UTR and 3'UTR and intronic regions covering the splice sites were PCR amplified and sequenced.
In the affected individuals of three Flemish families with the complete form of CSNB a novel NYX mutation, c.855delG was identified. This deletion is predicted to lead to a frameshift mutation, p.Asp286ThrfsX62 causing a premature stop codon.
Previously, both single families with different mutations in NYX as well as different families with an identical mutation, suggestive of a founder mutation, have been described. The c.855delG deletion in NYX seems to be a common mutation associated with CSNB in the Flemish population from Belgium. Thus, we suggest performing diagnostic testing for CSNB in the Flemish population initially directed towards the identification of this mutation. Subsequent screening for other mutations in NYX or GRM6 could be performed as a second step.

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Available from: Christina Zeitz
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    • "The retina-specific ECM protein nyctalopin, derived from the NYX gene, has been implicated in a form of CSNB (Bech-Hansen et al., 2000; Pusch et al., 2000) and the mouse " no b-wave " (NYX nob ) mutant (Gregg et al., 2003, 2007). Analysis of ERGs in CSNB patients and NYX nob mutant mice indicates a failure of transmission from photoreceptors to ON bipolar cells (Khan et al., 2005; Bahadori et al., 2006; Leroy et al., 2009). This is similar to effects of postsynaptic mutations in the glutamate receptor, mGluR6, or the transduction channel, TRPM1, at the ON bipolar synapse (McCall & Gregg, 2008; Shen et al., 2009; van Genderen et al., 2009; Koike et al., 2010; Morgans et al., 2010). "
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    • "Like mGluR6 and nyctalopin, TRPM1 is specifically enriched at dendritic tips and its elimination in mice completely abolishes ON-BC responses. Genetic association studies indicate that mutations in TRPM1 (Audo et al., 2009; van Genderen et al., 2009; Nakamura et al., 2010), mGluR6 (Zeitz et al., 2005; O'Connor et al., 2006) and nyctalopin (Bech- Hansen et al., 2000; Leroy et al., 2009) account for the majority of congenital night blindness cases in human patients. However, beyond general knowledge regarding the identity of the main players involved in ON-BC responses to light, our understanding of the mechanistic details pertaining to the organization of the signaling pathway is very limited. "
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