Isolated ocular disease is associated with decreased mucolipin-1 channel conductance.
OBJECTIVE
To evaluate a 15-year-old boy with MLIV (mucolipidosis type IV) and clinical abnormalities restricted to the eye who also had achlorhydria with elevated blood gastrin levels.


METHODS
In addition to a detailed neuro-ophthalmic and electrophysiological assessment, his mutant mucolipin-1 was experimentally expressed in liposomes and its channel properties studied in vitro.


RESULTS
The patient was a compound heterzygote for c.920delT and c.1615delG. Detailed neuro-ophthalmic 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 with wild-type mucolipin-1, whereas 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, whereas 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.
Goldin
Ehud
E
Molecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Caruso
Rafael C
RC
Benko
William
W
Kaneski
Christine R
CR
Stahl
Stephanie
S
Schiffmann
Raphael
R
D000126:Achlorhydria / Q000150:complications; D000293:Adolescent; D004596:Electroretinography; D005755:Gastrins / Q000097:blood; D017353:Gene Deletion; D006147:Guanine; D006579:Heterozygote; D006801:Humans; D008297:Male; D009081:Mucolipidoses / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D009154:Mutation; D051245:Retinal Bipolar Cells; D012164:Retinal Diseases / Q000175:diagnosis* / Q000209:etiology* / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D013941:Thymine; D050051:Transient Receptor Potential Channels
D005755:Gastrins; C416674:MCOLN1 protein, human; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; D006147:Guanine; D013941:Thymine