Mutations in gene TRAF7 are associated with a multisystem disorder

June 28, 2018, Baylor College of Medicine

A group of seven patients presenting with a similar disorder of unknown origin now know of a possible genetic root of their condition. A team of researchers sequenced all the protein-coding genes in the patients' genomes and identified four different mutations in the gene TRAF7. The researchers report in the American Journal of Human Genetics that in six individuals the mutations are de novo, meaning they are not present in the parents. Laboratory studies showed that the mutations resulted in a reduction of the normal activity of a cellular pathway called ERK1/2. Altogether, the results suggest that these mutations in TRAF7 are likely associated with the multisystem disorder presented by the patients.

"Our lab receives many samples for whole exome sequencing—the sequencing all the protein-coding genes—to try to identify the genetic cause of those ' diseases," said corresponding author Dr. Xia Wang, assistant professor of molecular and human genetics at Baylor College of Medicine and assistant laboratory director of Baylor Genetics. "When we analyzed the data of these patients, we did not find in genes that are known to cause certain diseases, but we found mutations in the gene TRAF7."

The seven patients share substantial overlap in the characteristics of their conditions; in particular, they present with developmental delay, , limb and digital anomalies as key unifying features.

"Finding gene mutations in a particular gene does not indicate that it is causing the . One way to show that the changes we found in gene TRAF7 could be causing the disease is to determine whether the mutations can affect the relevant signaling pathways associated with the gene," Wang said.

"We conducted extensive functional assays and showed that the mutations we identified in these patients can reduce the function of the signaling pathway ERK1/2," said co-first author Chun-An Chen, research assistant in molecular and in the Christian Schaaf lab. "I am excited that advanced and unbiased sequencing technologies can help us find variants of genes that could be causing the disease."

"Interestingly, previous work has shown that a change of function of the ERK1/2 pathway also is associated with a group of diseases called RASopathy, which share some features with the TRAF7-related disorders reported in this work," said Wang. "Further studies are needed to determine the possible mechanistic link between these two groups of diseases."

"The other notable observation is that other works indicate that mutations in TRAF7 also have been seen in cancer tissue," Wang said. "One of the oldest patients in our cohort did have a meningioma. TRAF7 joins the growing list of that are implicated in both cancer and human developmental disorders."

The researchers' next steps include finding more patients carrying variants in gene TRAF7 who present with similar clinical characteristics. Having more individuals would help better understand the connection of gene TRAF7 to this condition and help affected families and clinicians know what to expect when these children grow up.

Explore further: Gene ABL1 implicated in both cancer and a developmental disorder

More information: American Journal of Human Genetics (2018). DOI: 10.1016/j.ajhg.2018.06.005

Related Stories

Gene ABL1 implicated in both cancer and a developmental disorder

March 14, 2017
ABL1, a human gene well-known for its association with cancer now has been linked to a developmental disorder. The study, which was carried out by a team of researchers from institutions around the world, including Baylor ...

Team develops framework to identify genetic missense mutations linked to autism spectrum disorder

June 11, 2018
Missense mutations occur when there is a change in one gene's DNA base pair, and the change results in the substitution of one amino acid for another in the gene's protein. Mutations that disrupt the function of proteins ...

Unexplained developmental disorder linked to gene involved in essential cellular processes

August 18, 2016
A neurodevelopmental disorder for which there was no known cause has been linked to SON, a gene that is involved in essential mechanisms a cell uses to translate DNA into protein, as well as in DNA replication and cell division. ...

Newly identified gene mutation results in intellectual disability and developmental delay

April 12, 2018
An international group of researchers led by Cold Spring Harbor Laboratory (CSHL) Assistant Professor Gholson Lyon has identified a new genetic mutation associated with intellectual disability, developmental delay, autism ...

Mutations in CWC27 result in a spectrum of developmental conditions

March 10, 2017
An international team of researchers has discovered that mutations in the human gene CWC27 result in a spectrum of clinical conditions that include retinal degeneration and problems with craniofacial and skeletal development. ...

Genetic cause identified for previously unrecognized developmental disorder

December 22, 2016
An international team of scientists has identified variants of the gene EBF3 causing a developmental disorder with features in common with autism. Identification of these gene variants leads to a better understanding of these ...

Recommended for you

Gene editing possible for kidney disease

November 16, 2018
For the first time scientists have identified how to halt kidney disease in a life-limiting genetic condition, which may pave the way for personalised treatment in the future.

Progress in genetic testing of embryos stokes fears of designer babies

November 16, 2018
Recent announcements by two biotechnology companies have stoked fears that designer babies could soon be an option for those who can afford to pick and choose which features they want for their offspring. The companies, MyOme ...

DICE: Immune cell atlas goes live

November 15, 2018
Compare any two people's DNA and you will find millions of points where their genetic codes differ. Now, scientists at La Jolla Institute for Immunology (LJI) are sharing a trove of data that will be critical for deciphering ...

Ashkenazi Jewish founder mutation identified for Leigh Syndrome

November 15, 2018
Over 30 years ago, Marsha and Allen Barnett lost their sons to a puzzling childhood disease that relentlessly attacked their nervous systems and sapped their energy. After five-year-old Chuckie died suddenly in 1981, doctors ...

Drug candidate may recover vocal abilities lost to ADNP syndrome

November 15, 2018
Activity-dependent neuroprotective protein syndrome (ADNP syndrome) is a rare genetic condition that causes developmental delays, intellectual disability and autism spectrum disorder symptoms in thousands of children worldwide. ...

The puzzle of a mutated gene lurking behind many Parkinson's cases

November 15, 2018
Genetic mutations affecting a single gene play an outsized role in Parkinson's disease. The mutations are generally responsible for the mass die-off of a set of dopamine-secreting, or dopaminergic, nerve cells in the brain ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.