[Week 4: Feb. 24-28] Mucolipidosis type IV

Here's some info on mucolipidosis type IV, the disease my lab's resesarching. Feel free to ask questions if anything's unclear.

Introduction
Mucolipidosis type IV is a genetic disease with autosomal recessive inheritance pattern. The disease affects nerves and the eyes. Patients with it frequently present with "delayed development and impaired vision" (U.S. National Library of Medicine®). There are two forms: typical mucolipidosis type IV(the severe form) and atypical mucolipidosis type IV (the less severe form). Around 90% of affected patients have typical mucolipidosis type IV.

Symptoms

• Psychomotor delay (taking longer to develop mental skills and coordination)
•  Problems with controlling muscle movement that can worsen over time
• Impaired vision which can develop into blindness
• Clouding of the cornea, the outermost layer at the front of the eye
• Death of the light-sensitive cells of the retina
• Achlorhydira
• Reduced production of stomach acid
• Results in abnormally high levels of gastrin the blood 
• Doesn't really cause much else in this case
• Iron deficiencies which can result in anemia (not enough red blood cells)

Patients with atypical mucolipidosis type IV have less severe symptoms.

Causes
Mucolipidosis is caused by mutation(s) in the gene Mucolipin 1 (MCOLN1) on chromosome 19. MCOLN1 codes for the protein MCOLN1 which is involved in transporting materials in and out of endosomes and lysosomes. Its regular function and the specifics of how it mutated MCOLN1 leads to developing symptoms of mucolipidosis type IV  is not entirely understood. Individuals with mutated MCOLN1 have abnormally large lysosomes and their neurons die.  

In the lab
The nematode C. elegans has an orthologue to MCOLN1: the gene CUP-5. Nematodes with mutated CUP-5 also present with abnormally large lysosomes. Those with mutated CUP-5 can lay eggs, but their eggs never hatch because the embryos die; however, if they're given MCOLN1 (from humans) then they can survive and become what's called a "rescue."

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Sources

1. U.S. National Library of Medicine®. (2013). Mucolipidosis type IV. Retrieved from U.S. National Library of Medicine® Genetics Home Reference website: http://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv
2. U.S. National Library of Medicine®. (2009). MCOLN1. Retrieved from U.S. National Library of Medicine® Genetics Home Reference website: http://ghr.nlm.nih.gov/gene/MCOLN1