Isolated Ocular Disease is Associated with Decreased Mucolipin-1 Channel Conductance
Ehud Goldin 1,
Rafael C Caruso 2,
William Benko 3,
Christine R Kaneski 3,
Stephanie Stahl 3,
and
Raphael Schiffmann 4*
1 Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States
2 Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
3 Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, United States
4 Developmental and Metabolic Neurology Branch, National Institutes of Health, National Institute of Neurological Disorders and Stroke, Bldg. 10, Rm. 3D03, Bethesda, Maryland, 20892-1260, United States; Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, Texas, 75226, United States
* To whom correspondence should be addressed. E-mail: rs4e{at}nih.gov.
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Abstract |
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Purpose. To evaluate a 15-years-old male with MLIV and clinical abnormalities restricted to the eye that also had achlorhydria with elevated blood gastrin levels. Methods. In addition to a detailed neuro-ophthalmological and electrophysiological assessment, we expressed his mutant mucolipin-1 in liposomes and studied in vitro its channel properties.
Results. The patient was a compound heterzygote for c.920delT and c.1615delG. Detailed neuro-ophthalmological examination including electroretinography showed him to have a typical retinal dystrophy predominantly affecting rod and bipolar cell function. In vitro expression of MCOLN1 in liposomes showed that the c.1615delG mutated channel had significantly reduced conductance compared to wild-type mucolipin-1, while the inhibitory effect of low pH and amiloride remained intact.
Conclusions. These findings suggest that reduced channel conductance is relatively well tolerated by the brain during development while retinal cells and stomach parietal cells require normal protein function. MLIV should be considered in patients with retinal dystrophy of unknown cause and screened for using blood gastrin levels.
Key Words:
Ca2+ channels, evoked potentials, retinal dystrophy, electroretinography
