Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked congenital stationary night blindness (CSNB) is a recessive non-progressive retinal disorder characterized by night blindness, decreased visual acuity, myopia, nystagmus and strabismus. Two distinct clinical entities of X-linked CSNB have been proposed. Patients with complete CSNB show moderate to severe myopia, undetectable rod function and a normal cone response, whereas patients with incomplete CSNB show moderate myopia to hyperopia and subnormal but measurable rod and cone function. The electrophysiological and psychophysical features of these clinical entities suggest a defect in retinal neurotransmission. The apparent clinical heterogeneity in X-linked CSNB reflects the recently described genetic heterogeneity in which the locus for complete CSNB (CSNB1) was mapped to Xp11.4, and the locus for incomplete CSNB (CSNB2) was refined within Xp11.23 (ref. 5). A novel retina-specific gene mapping to the CSNB2 minimal region was characterized and found to have similarity to voltage-gated L-type calcium channel alpha1-subunit genes. Mutation analysis of this new alpha1-subunit gene, CACNA1F, in 20 families with incomplete CSNB revealed six different mutations that are all predicted to cause premature protein truncation. These findings establish that loss-of-function mutations in CACNA1F cause incomplete CSNB, making this disorder an example of a human channelopathy of the retina.
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PMID:Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. 966

X-linked CSNB patients may exhibit myopia, nystagmus, strabismus and ERG abnormalities of the Schubert-Bornschein type. We recently identified the retina-specific L-type calcium channel alpha1 subunit gene CACNA1F localised to the Xp11.23 region, which is mutated in families showing the incomplete type (CSNB2). Here, we report comprehensive mutation analyses in the 48 CACNA1F exons in 36 families, most of them from Germany. All families were initially diagnosed as having the incomplete type of CSNB, except for two which have been designated as Aland Island eye disease (AIED)-like. Out of 33 families, a total of 30 different mutations were identified, of which 24 appear to be unique for the German population. The mutations, 20 of which are published here for the first time, were found to be equally distributed over the entire gene sequence. No mutation could be found in a classic AIED family previously shown to map to the CSNB2 interval. Cacna1f expression in photoreceptor-negative mice strains indicate that the gene is expressed in the outer nuclear, the inner nuclear, and the ganglion cell layer. Such a distribution points to the central role of calcium regulation in the interaction of retinal cells that mediate signal transmission.
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PMID:Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina. 1211 38

Congenital stationary night blindess-2 (incomplete congenital stationary night blindness (iCSNB) or CSNB-2) is a nonprogressive, X-linked retinal disease which can lead to clinical symptoms such as myopia, hyperopia, nystagmus, strabismus, decreased visual acuity, and impaired scotopic vision. These clinical manifestations are linked to mutations found in the CACNA1F gene which encodes for the Ca(v)1.4 voltage-gated calcium channel. To better understand the physiological effects of these mutations, three missense mutants, F742C, G1007R and R1049W, previously shown to be mutated in patients with CSNB-2, were transiently expressed in human embryonic kidney (HEK) tsA-201 cells and characterized using whole-cell patch clamp. The G1007R mutation is located in transmembrane segment 5 (S5) of domain III and R1049W is located in the extracellular linker between S5 and the P-loop of domain III. Both mutants produced full length proteins that targeted to the membrane but did not support ionic currents. In 20 mM Ba(2+), F742C (S6 domain II) produced a approximately 21 mV hyperpolarizing shift in half activation potential (V(a[1/2])) and a approximately 23 mV hyperpolarizing shift in half inactivation potential (V(h[1/2])). Additionally, F742C displayed slower inactivation kinetics and a smaller whole cell conductance (G(max)). In physiological 2 mM Ca(2+), F742C produced a approximately 19 mV hyperpolarizing shift in V(a[1/2]). These findings suggest that the pathology of CSNB-2 in patients with these missense mutations in the Ca(v)1.4 calcium channel is the result in either a gain of function (F742C) or a loss of function (G1007R, R1049W).
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PMID:Functional analysis of congenital stationary night blindness type-2 CACNA1F mutations F742C, G1007R, and R1049W. 1794 18