I (Denise) am the mother of a lovely, vivacious 23 year-old woman with autism. She is good natured and is noticeably happy for the most part, but has minimal communication ability, intractable seizures and motor problems.
Her autism became apparent at around two years old in 1997; she had pretty normal development to that point, but started slipping away. With her regression, she lost all language and much of the fine motor skills she had acquired. She received a diagnosis of autism at 27 months. Some notable childhood traits included a large forehead, abnormal bone development, joint hypermobility, late development of gross motor skills, an abnormal EEG, and sensory challenges (she hated the sound of a large outdoor fountain that was near our home). As a baby, she did not seem bothered by her motor challenges; she was happy and content to walk at a 13 months holding onto our hands, but did not walk alone until 17 months. Unfortunately, by age two it was apparent that her skills had stealthily declined and she experienced the disturbing loss of eye contact and initiated stereotypic behaviors like spinning and odd hand movements often seen in autism.
Like most people diagnosed with autism she was tested for chromosomal abnormalities as a child — this test was normal. A test for Rett Syndrome also came back normal.
Fourteen years later, in 2011, our family was able to get an appointment with a clinical geneticist interested in autism. He mentioned genetic testing as a future plan. Then it took until 2014 to arrive at being considered for exome sequencing. This is a genetic test that looks for mutations in that 1% protein-coding portion of the genome. Insurance gave clearance after a few months. We did the testing as a "trio," meaning that my husband, myself, and daughter all submitted blood samples. We did the testing through Stanford, where I work.
After a few months the results came back... with nothing important to tell us. There was a missense mutation found, but it was not known to be pathogenic, even I had that same mutation.
Then more than a year later, in Dec 2015, our family got an interesting phone call from the geneticist. A de novo germline mutation was found in our daughter's genome. The mutation was on chromosome 1, and concerns a gene called GNB1.
In 2015, a team at Columbia University identified the first few cases of individuals with a mutation in GNB1. Columbia then queried genetic repositories worldwide and found a total of 13 individual with this mutation. The Columbia researchers published a paper sharing their amazing findings in April 2016.
During our fateful call in 2015, our geneticist also ventured to add that he thought the GNB1 mutation was the cause of our daughter’s autism. Wow, autism explained – in our case, the explanation is an identified rare disease that has autism as one of its features.
I’ve always been driven, but now I have a mission with a solid direction. I now have knowledge of what is causing my daughter's many challenges and symptoms. Rather than addressing that amorphous thing we call "autism," I can instead direct my attention to her particular disorder and its biological pathways. Rather than treating autism, we can support research on pharmaceutical treatments that target blocking or unblocking receptors and signals that aren't working in our daughter's specific syndrome.
"Rather than addressing that amorphous thing we call 'autism,' I can instead direct my attention to her particular disorder and its biological pathways."
​This mutation is noted to be disease causing (though it does not cause autism symptoms in all cases) and we know the mutation affects many bodily systems. Through the years, she has had many symptoms of some sort of unknown underlying illness – a general malaise that could not be pinpointed. We now know that her chronic hematological abnormalities through the years likely stem from the mutation and unfortunately, is an ominous symptom to follow as she ages. We can explore what her mutation does to the body’s chemistry that may influence her seizures. Her treating physicians can help us to use medicine to prevent potential health problems that are unique to people who have this mutation. She fits a particular mold, which we now recognize and better understand.
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My short-term hope is to find the cause of seizures that many of the individual with the mutation experience. These seizures are often life-threatening and must be avoided. In the long term, I hope research unveils the cell signaling that is dictated by the GNB1 gene which will advance our understanding of the pathogenesis of the mutation and human biology in general.
Like everything in autism, nothing about this mutation is straightforward. Individuals with glitches in GNB1 present with a spectrum of features, from verbal to non-verbal, ambulatory to non-ambulatory, and having sensory challenges of differing degrees depending on where the mutation is located on the gene. Knowing that defects within one single gene can seed such a dizzying array of phenotypes should give us pause when we even think of “autism” as a unitary disorder.
But we also have a great deal in common, and connecting with other GNB1 families has been nothing short of amazing. I get emotional just writing about it. I see photos of the young children with this mutation, and I worry. Many have not yet developed seizures but unfortunately may do so as they age. We must assist these parents so that they can take preventive measures to avoid their child’s exposure to seizures. I feel empowered with this newfound information and motivated to nth degree to understand more.
Now, I am not a Facebook fan (in fact, I am a bit of a hater) but I must say that for our families, it’s been the best thing EVER. A parent set up a GNB1 disorder private group that now includes families from more than 10 countries. We share all sort of information about our kids that help us evaluate trajectory and interventions. We are also working on a GNB1 website that is about to go live (gnb1.org)
I want to encourage all autism families to undergo genetic testing. We must remember that as parents, we help guide our loved one’s care – so please ask for testing and follow-up on the process. Ask who you should call to follow-up on the authorization process and call monthly (I would like to encourage follow-up calls – the insurance process can be difficult and clinicians have large caseloads). Do not feel shy about asking for testing, and insisting — you are your loved one's absolute best advocate.