Most of the neurodegenerative diseases that we have been studying are those affecting mostly the elderly, however I was curious about neurological disorders that affect children and how they develop. I came across a devastating disease called Mucolipidosis Type IV which is a genetic neurodegenerative disease resulting in progressive vision loss and delayed mental and motor skills. However, even though this disease is fairly rare, about 70% of those affected individuals have Ashkenazi Jewish ancestry. Why?
ML4 is an autosomal recessive lysosomal storage disorder caused by a mutation on the MCOLN1 gene. This gene is responsible for creating the protein mucolipin-1 which is found in membranes of lysosomes and endosomes. Mucolipin-1 is responsible for (although not completely understood) transporting fats and proteins between lysosomes and endosomes that proves necessary for the development and support of the brain and retina. A mutated mucolipin-1 causes nonfunctional transfer and communication which leads to a buildup of substances inside the lysosomes, which is why it is called a lysosomal storage disorder.
Unfortunately, about 1 in 100 Ashkenazi Jews are carriers of the defected MCOLN1 gene but the carrier rate in the general population is unknown. Children born with this gene will develop no further than a 15-month old in language and motor function. In addition to neural and vision problems, those affected will also experience digestive problems because mucolipin-1 also plays a role in the production of digestive acids.
However, there is hope! With early intervention and intense therapy, children may show less degeneration and more independence. For example, the 5-year old girl in the following picture was diagnosed with ML4 was able to sit up on her own with minimal support and had no obvious vision problems.
http://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv
http://www.ml4.org
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824620/ (picture)
http://www.jewishgeneticdiseases.org/diseases/mucolipidosis-type-4/
This is a very interesting mutation that you decided to talk about. I looked it up, and found that "Mucolipidosis type IV is estimated to occur in 1 in 40,000 people. About 70 percent of affected individuals have Ashkenazi Jewish ancestry." Do you have any idea how long this mutation has been around? I find it peculiar that a majority of the population with this mutation are in the Ashkenazi Jewish population.
ReplyDeleteSource:
http://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv
I thought the same thing! I found a website that says that it was first described in 1974 but I feel like it has been around for a while longer....
Delete(http://www.mazornet.com/genetics/ml4.htm)
I figured after reading this interesting post and your reply that I might do a little investigating myself. I first thought that the reason this disease might be so apparent in the Ashkenazi Jewish population would be because of the location of ancestors.
DeleteWhat I found was that a study of haplotypes of the Y-chromosome, published in 2000, addressed the paternal origins of Ashkenazi Jews. They found that "the Y-chromosome of Ashkenazi and Sephardic Jews contained mutations that are also common among Middle Eastern peoples, but uncommon in the general European population suggesting that the male ancestors of the Ashkenazi Jews could be traced mostly to the Middle East."
However, in 2002 a gentleman named David Goldstein reported that, unlike male lineages, the female lineages in Ashkenazi Jewish communities "did not seem to be Middle Eastern", and that each community had its own genetic pattern and even that "in some cases the mitochondrial DNA was closely related to that of the host community." In his view this suggests "that Jewish men had arrived from the Middle East, taken wives from the host population and converted them to Judaism, after which there was no further intermarriage with non-Jews."
I realize that this just makes things more confusing, but it is interesting nonetheless.
Reference:
Hammer, M. F.; A. J. Redd, E. T. Wood, M. R. Bonner, H. Jarjanazi, T. Karafet, S. Santachiara-Benerecetti, A. Oppenheim, M. A. Jobling, T. Jenkins, H. Ostrer, and B. Bonné-Tamir (9 May 2000). "Jewish and Middle Eastern non-Jewish populations share a common pool of Y-chromosome biallelic haplotypes". Proceedings of the National Academy of Sciences 97 (12): 6769. Bibcode 2000PNAS...97.6769H. doi:10.1073/pnas.100115997. PMC 18733. PMID 10801975.
Wade, Nicholas (14 January 2006). "New Light on Origins of Ashkenazi in Europe". The New York Times. Archived from the original on 23 May 2006. Retrieved 24 May 2006.
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ReplyDeleteTay Sachs disease is also common amongst the Ashkenazi Jewish population as well. In fact the Tach Sachs mutation on Chromosome 15 is the most common mutuation among Ashkenazi Jews at a prevalence of 1 in 3500. Tay Sachs is also due to a problem within the phospholipid membrane and sufferes from Tay Sachs face some of the same degenerative neurological problems as ML4 patients. I wonder if there's a contection between ML4 and Tay Sachs within the gene pool. In general Sphingolipidose (lipid storage disorders) like Tay Sachs are much more common in the Ashkenazi Jewish population.
ReplyDeleteI tend to agree with you that this has probably been around for much longer than when it was first described. I went hunting for you but could only turn up little evidence just pointing to, "Prior to the availability of molecular diagnosis of mucolipidosis IV, individuals with atypical mucolipidosis IV were thought to have cerebral palsy, suggesting that mucolipidosis IV is underdiagnosed." Which would make sense since the variations of mutations and severity of symptoms, that pre molecular genetics this would be thought to have cerebral palsy or a variation of PMR.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/books/NBK1214/
http://ghr.nlm.nih.gov/condition/mucolipidosis-type-iv
It is important to note the the Ashkenazi Jewish population tended to be very close-knit and as a result, tended to have more inter-marrying within its families. For the lack of a better term, they are somewhat "inbred" and tend to have many odd diseases because of this. Many Ashkenazi Jews had certain unique psychological disorders as well, which made them a popular group to study for many psychologists that would go on to create the foundations of psychoanalysis (Late 1800s-Early 1900s). In a book on the history or psychoanalysis titled "Revolution in Mind," a decent amount of text is spent on the Ashkenazi Jewish population, and their small gene pool is mentioned. Just thought I'd add this tidbit of info.
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