Researchers from the Developmental Biology Institute of Marseille and the University of Manchester have identified a link between autism spectrum disorder and abnormal kidneys in children born with a deleted TSHZ3 gene. Their gene research study findings were published September 26 in the journal Nature Genetics.
The TSHZ3 gene region is critical for a syndrome associated with heterozygous deletions at 19q12-q13.11. This syndrome includes autism spectrum disorder. The researchers for this study discovered a patient with this gene deletion who was born with abnormal kidneys and who displayed autism spectrum disorder behaviors. They then reviewed past research in mice and discovered that the mice with this gene deletion not only had kidney problems but also ASD-like learning difficulties. A global search of kidney clinics was then done which found 10 more patients with similar symptoms of abnormal kidneys and autism spectrum disorder behaviors where genetic testing subsequently revealed the deletion of the TSHZ3 gene. The researchers concluded that their gene research findings demonstrate how the TSHZ3 gene is essential for brain cerebral cortical projection neuron (CPN) development and function.
Sources: Genengnews.com (Genetic Engineering & Biotechnology News), Sept. 27, 2016.
Nature.com: “TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons,” Sept. 26, 2016.
Pitt-Hopkins Syndrome, which is present at birth or develops in early childhood, is caused by mutations in the TCF4 gene located on chromosome 18q21.2. There are reportedly only 500 cases of the syndrome in the world though it is thought the syndrome may be underdiagnosed. One of the major reasons for this likely underdiagnosis is the syndrome has many characteristics that are also associated with autism spectrum disorders; although there are other distinctive features of the syndrome as well.
Like autism spectrum disorders, many of those with Pitt-Hopkins Syndrome have delayed development of mental and motor skills. People with the syndrome typically do not develop speech or learn only a few words. Delays often occur in learning to walk. Additionally, their demeanor is “typically … happy, excitable…with frequent smiling, laughter and hand-flapping movements.” Those with the syndrome commonly experience “anxiety and behavioral problems;” and they may also experience recurrent seizures.
Some unique features of Pitt-Hopkins Syndrome are breathing problems and certain facial and ear characteristics. The breathing problems can fluctuate between hyperventilation and slowed breathing or even apnea and may be triggered by “fatigue, anxiety or excitement.” The distinctive facial features are “thin eyebrows, sunken eyes, a prominent nose with a high nasal bridge, a pronounced double curve of the upper lip called Cupid’s bow, wide mouth with full lips and widely spaced teeth.” Additionally, the ears may be “thick and cup-shaped.”
A recent gene research breakthrough that may lead to a treatment for Pitt-Hopkins Syndrome was discovered by scientists at the Johns Hopkins University-affiliated independent laboratory, the Lieber Institute for Brain Development. The researchers studied the brains of rats affected by Pitt-Hopkins Syndrome and found “alternative channels in the brain interrupting normal cell activity.” The gene research showed these interruptions caused inappropriate responses to stimuli in the environment. Further, the researchers discovered a drug being “investigated for use on chronic pain” that blocked these alternative channels resulting in cells behaving normally. However, at this point, researchers are not sure what restoring normal cell activity would do to those with the syndrome but are hopeful that some of the deficits could be eliminated.
Sources: CapitalGazette.com of March 11, 2016.
Ghr.nlm.nih.gov; “Pitt-Hopkins Syndrome;” Last reviewed February 2015.
Johns Hopkins University School of Medicine reported in the Journal Nature in March of this year about a study by a professor at the school, Aravinda Chakravarti, regarding an autism gene research breakthrough he and his team found. Their research focused on the gene CTNND2. Chakravarti et al compared the gene sequences of 13 families who had more than one female with autism spectrum disorder to the gene sequences of people from a “public database.”
The researchers found four potential genes that could be implicated in autism but they focused on the CTNND2 gene because it was found in a region of the genome “known to be associated with another intellectual disability.” They then studied the “gene’s effects in zebrafish, mice and cadaveric human brains.” Their gene research noted that the protein the gene made affected how “many other genes are regulated.” This CTNND2 gene protein was found in fetal brains far more often than in adult brains so the researchers postulated that the gene plays a key role in brain development.
Chakravarti and his team note that autism-causing variants in the CTNND2 gene are very rare. Nevertheless, they believe their gene research is helpful in learning the “general biology of autism.” The research team is now working to find out what the functions of the other three genes are that they believe may possibly be associated with autism.