All posts by Puneet Rai

“Best Practices in PKAN” is now published!

Our team is excited to announce that we and several of our collaborators have developed a set of guidelines called “Best Practices in PKAN.” These guidelines provide recommendations and instructions for taking care of a child or adult with PKAN. They will be a valuable resource for patients themselves and for any doctors they may see who are not familiar with PKAN.

The document has been published in a scientific journal and you can access it here:

Upcoming: The 2017 NBIA Scientific Meeting

This upcoming scientific meeting will allow researchers studying NBIA disorders to come together to share their findings, discuss potential therapeutics and plan projects/collaborations. The 6th International Symposium on NBIA & Related Disorders will taken place April 7th-8th, 2017 at Skamania Lodge in Stevenson, WA.

If you are a researcher studying NBIA and related disorders, please follow the link below to learn about registration, lodging, abstract submission and applying for an Early Career Investigators travel award.

Important deadlines:

Application for an Early Career Investigator travel award is due December 1, 2016
Early conference registration (discounted price) ends on December 31, 2016
Abstract submission is due January 16, 2017
Deadline for hotel reservations at discounted price is February 1, 2017

6th International Symposium on NBIA & Related Disorders

Note for NBIA families:
This conference was established for researchers and presentations/talks will be geared towards a scientific audience. However, if a non-researcher still wants to attend, we will not prohibit them from coming. Also, we will share important updates that come out of this scientific meeting at the NBIA Disorders Family Conference in 2017.

Summary of 2016 BPAN Research Meeting

A summary of the 2016 BPAN Research Meeting in Portland is now up on our website! Check it out to learn about what we did, see lots of pictures of the wonderful children and families who attended and read the research updates we shared at the symposium. We can’t say thank you enough to everyone who provided biological samples at the meeting. Those cells are hard at work in our research studies and with our collaborators in England. Have you ever been to London? Well now your children’s cells have!

In addition, our team learned there were many advantages to holding a research meeting in Portland so we will likely be replicating this type of meeting in the future for other NBIA disorders.


PKAN Best Practices Feedback Request

Last year at the family conference, Dr. Hayflick announced that work had begun on a set of guidelines called “Best Practices in PKAN” that would provide recommendations and instructions for taking care of a child or adult with PKAN. This project was funded by the NBIA Disorders Association, Hoffnungsbaum, e.V., and Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro. After collaborating with knowledgeable specialists in various fields, such as neurology, nutrition, ophthalmology, and physical therapy, these guidelines are almost ready to submit for publication.

Before we submit this to a scientific journal, we would like to get input from you, the families who live with and manage PKAN every day. Your personal experiences will add valuable insight and help us create a set of gold standards for the diagnosis and management of PKAN.

You can request a copy of the best practices guideline by emailing Feedback is due back in 2 weeks on July 12th.

Announcement: 2016 BPAN Research Meeting!


Our team is excited to announce that we will be hosting a BPAN research meeting in Portland, Oregon from June 24th-26th! We are thrilled to welcome you to our hometown and have planned a variety of activities including research activities, social events, a mini-symposium, and individual appointments with Dr. Hayflick and Dr. Hogarth.

For more details, please visit the event page here:

Once you have made travel plans, please contact us directly ( and let us know when you will arrive and where you will stay. Then, we can schedule appointment times with you for the individual parts of the research weekend.

Ask Jeff: The Mouse Expert Replies

You may recall that back in September we asked if anyone had questions about the PKAN knock-in mice for our resident mouse wrangler, Jeff. We had one curious dad who submitted some very interesting questions (and a few amusing ones that gave our team a good laugh). So without further ado, here are some answers:

Q1. Is the defect identical on both genes or are there two different ones mixed together?

The mutation in both of their PANK2 genes is the same. This allows us to have consistency in their behavior. One can imagine that if one particular mutation is more damaging to the PANK2 gene than another that would make things quite confusing for testing.

Q2. How do you ensure there are no other genetic spontaneous or inherited conditions causing symptoms?

All mice are bred on a specific genetic “background”. Basically, that means that they’re all a standard breed of mouse, in the same way that Jack Russell terriers are a standard breed of dog. The mice are identical except for the PKAN-causing mutations. To make sure they stay that way, we periodically order certified mice of that breed from a company and mate them with our colony. That allows us to minimize any outside spontaneous genetic conditions.

Q3. How do you get your mice to fall over backwards if they have four legs?

When we evaluate humans with PKAN, we measure their balance and coordination by having them do tests like walking a short distance or standing with their eyes closed. However, with PKAN mice, we use a different method called the rotarod performance test. A rotarod is a rotating cylinder as seen in the image below. Basically, the mice are placed on the rotarod and we see how well they’re able to stay perched on that cylinder. Mice with movement disorders, like PKAN, tend to fall off quickly.
Image courtesy of

Q4. Do the mice get headphones in the MRI? What music do you play them?

We don’t use MRIs to evaluate the mice’s brain, but if we did, I imagine the “Mighty Mouse” theme song would be a favorite :)

Unexpected Family Ties

NBIA in Africa? We don’t often hear about new NBIA diagnoses in African countries. The NBIA disorders are not isolated to a particular race or ethnicity so we know individuals must be diagnosed in countries all over the world. Genetic testing is more widely used each year but having affordable access to it is still a barrier in many parts of the world. There are likely many individuals with NBIA in African countries who are still undiagnosed. Another reason we don’t hear as often about these individuals is that identified cases may not be getting published and shared with the global community. That is just one reason why this new study out of North Africa is so fascinating!

PLAN Testing in North Africa

In a study by Romani et al. (2015), seventeen patients (10 girls and 7 boys) from 13 unrelated families had genetic testing of the PLA2G6 gene. This testing was done because the children were all suspected of having infantile-onset PLAN (PLA2G6-associated neurodegeneration) due to their symptoms. The PLA2G6 gene is currently the only gene known to cause all the types of PLAN. The seventeen patients came from eleven families in Tunisia, one from Algeria and one from Libya. As the map below shows, these countries are located next to each other along the southern border of the Mediterranean Sea.


After completing genetic testing, the researchers discovered that five of the families from Tunisia and one family from Libya had the exact same mutation (p.V691del) in the PLA2G6 gene. By analyzing the size and location of the mutation and the number of families sharing the mutation, the study team estimated that this genetic change first occurred in a distant relative shared by these families at least 12 generations back! Assuming that women in each generation had children around 25-30 years of age, this common ancestor likely lived around the late seventeenth century (or even earlier).

In the case of many other genetic diseases, individuals who are affected may pass away before reproducing and this stops the mutation from reaching future generations. However, in the case of autosomal recessive conditions, like PLAN, individuals with just one mutation have no symptoms and that mutation can be passed through multiple generations without any individuals being affected. It is only when two individuals with mutations (the same mutation or different mutations) in the same gene have children together that an affected individual may first appear in the family.

Based on these facts, the study speculated that the one common ancestor of all these families, who lived somewhere around the Mediterranean Sea in the late seventeenth century, was the first to spontaneously develop the p.V691del mutation in their PLA2G6 gene and then passed it on to his/her children, who then passed it on to their own children, and so forth. This phenomenon is called a “founder mutation.”

What is a founder mutation?

It is a gene mutation that is observed with high frequency in a group that is or was geographically or culturally isolated, in which one or more of the ancestors was the first carrier of that mutation.

How do founder mutations occur?


In many cultures, especially in the older generations, marriage practices such as consanguinity and endogamy increased the prevalence of founder mutations in certain populations. Consanguinity is the practice of marrying within a family, such as first or second cousins getting married. Endogamy is the practice of marrying within a specific ethnic group, religion, class, or social group. These practices, along with population decrease, migration or geographical isolation, can increase the number of individuals within a population who carry (and pass on) the same founder mutation. In the case of the Tunisian and Libyan families with the same PLAN mutation, so many years had passed since the founder mutation first occurred that many of them had no idea they were related! After all, not many of us know our ancestry going back over four hundred years ago.

How common are founder mutations?

Founder mutations are actually fairly common among humans. There are many communities around the world in which multiple disease-causing founder mutations have been identified. Some well known examples include the Amish, French-Canadian and Ashkenazi Jewish. These communities have a high rate of founder mutations because they were established by a limited number of founders and tend to marry within their community.


The families in the 2015 study by the Romani et al., had genetic testing done to try to figure out the cause of their children’s symptoms. They never could have imagined the other surprising discovery made about their shared ancestry through this testing! Interestingly, the p.V691del in the PLA2G6 gene has also previously been identified in a family from Jordan and two families from Israel. Just how far does this family tree expand?


Source article: “Infantile and childhood onset PLA2G6-associated neurodegeneration in a large North African cohort” by Romani et al. (2015).

Original map source:

Our PKAN mice have news to share

This has been an exciting month for our mice! In September, a new litter who we have been eagerly anticipating was born in the Hayflick lab.

As you may recall from one of the past NBIA Disorders Association newsletters, the Hayflick lab is developing a new mouse model for NBIA. This mouse has been genetically engineered to have a mutation in Pank2, the gene that causes PKAN, and mimics mutations seen in people with the disease.


Getting the mice to the point where they can be used for experiments has been a time-consuming process, but the good news is that we’re finally almost done! The last pairs of breeding mice were set up, and in the past week or so, they gave birth to experiment-ready mice. This is a very big step for our lab, not only for our personal efforts, but hopefully for developing new knowledge about NBIA in general.

Do you want to learn more about the PKAN knock-in mice? Do you have any burning questions about the process so far or what’s coming up in the future? You can now directly ask our resident mouse expert, Jeff! He has graciously agreed to answer questions submitted to our Facebook, Twitter or by email to Send in your mouse questions!


In about 1-2 weeks, we will make another post with Jeff’s answers for everyone to read.

PKANready Launches!

Those of you who attended this year’s NBIA Disorders family conference may recall Dr. Hayflick, Dr. Hogarth and Allison emphasizing how important it is to collect natural history data in order to get the NBIA community ready for any drug trials that may be coming down the pipeline. We are now taking the first step to making that goal a reality and are proud to launch PKANready! This is a five-year clinical study that will help us better understand the natural history of PKAN (how symptoms appear and change over time) and hopefully identify disease markers that can be used in future clinical trials. We will be starting with the PKAN community but this study will soon expand to the other NBIA disorders as well.


OHSU Launches New NBIA Testing Panel

The NBIAcure team has exciting news to share! The Knight Diagnostic Lab at OHSU has launched a brand new panel that can test for all the NBIA disorders at once. This panel can be a useful diagnostic tool when an individual suspected of having NBIA has symptoms that don’t match just one NBIA disorder. Our understanding of the NBIA disorders is always evolving, and the spectrum of symptoms for certain disorders is expanding with each new diagnosis. Individuals who may not have been diagnosed based on our previous knowledge are now being identified using new technology, like this NBIA panel. Along these same lines, this new test can also be useful in cases when an individual suspected of having NBIA has already tested negative for one or two forms of NBIA. Rather than doing testing for each disorder one by one, which can be time consuming and expensive, the individual could be tested for all the NBIA disorders at once with a single test.

If you are a clinician, the link below will take you to the Knight Diagnostic Lab’s page for the NBIA panel. It includes additional information about the test and how to order it. Only a physician can order this test, so if you are interested in this test for yourself or a family member, please talk to your doctor.

The NBIA Panel

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