Newly identified gene mutation results in intellectual disability and developmental delay

April 12, 2018, Cold Spring Harbor Laboratory
Genetic pedigrees of 3 families with individuals with familial or de novo (spontaneous) mutations in the NAA15 gene. The mutations caused different impacts (called phenotypes by scientists) in each of the affected individuals. So far, 37 individuals in 32 families have been found to have the newly identified illness. Credit: Lyon lab, CSHL

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 spectrum disorder, abnormal facial features, and congenital cardiac anomalies.

The genetic mutation, which can run in families, is related to the mutation underlying Ogden syndrome, a much more serious condition that shares many of the same symptoms.

In 2011, Lyon and his colleagues published the first paper about Ogden syndrome, named for the Utah town in which five boys across two generations of a single family were struck down by the disease before age 3. Caused by a mutation in a gene called NAA10, Ogden is an X-chromosome-linked condition, meaning only males are afflicted.

In the years since Ogden's discovery, Lyon has been collecting information on individuals with mutations in a related gene called NAA15. It bears the blueprint for a protein that works alongside the NAA10 protein in a cellular mechanism that modifies other proteins. This mechanism is called NatA-mediated N-terminal acetylation.

Lyon was made aware of the first individual with what he calls "NAA15-related disorder" by clinical geneticist Wendy Chung at Columbia University. She and colleagues had published a paper in which they described a boy with a mutation in NAA15 who had as well as developmental delays and . Lyon and colleagues have since collected referrals from clinicians around the world that have identified a total of 37 individuals in 32 families with a mutation in NAA15. They include both men and women, as the NAA15 gene is not located on the X chromosome. Dr. Holly Stressman of Creighton University and Dr. Linyan Meng of Baylor College of Medicine were co-senior leaders of the team, with Dr. Lyon.

Schematic representation of the genomic structure of human NAA15, where solid blue rectanglesindicate exons and the horizontal bars represent introns. Exons are the portion of the gene that contain instructions for making protein; introns are the intervening segments, which are ultimately edited out of the RNA that carries the gene's message to cellular protein factories. NAA15 variants with their relative positions in the gene are shown and the number of affected individuals with the specific variants are shown in parenthesis. Credit: Lyon Lab, CSHL

"Trying to prove the relevance of any mutation in a gene requires a large number of samples," Lyon says. "As a result, we're seeing the field of human genetics move more toward this type of large-scale collaboration." This points to the future promise of this research, he suggests. "As the price of genetic sequencing drops and more people are sequenced, we may be able to provide individuals with such mutations with more education and services in early life which could lead to better overall functioning."

Lyon expects that many more disorders caused by rare mutations like NAA15 will be discovered. "Instead of lumping many diseases together under very broad categories like 'intellectual disability' or 'autism,' the human genetics community is now splitting these into much finer entities so that we can begin to do natural history studies, much like what has been done with Fragile X syndrome," he says, citing the progress in understanding Fragile X based on extensive examinations of in the FMRP gene associated with that disease.

Explore further: Discovery of X-linked intellectual disability syndrome is aided by web tools

More information: Cheng H et al, "Truncating variants in NAA15 are associated with variable levels of intellectual disability, autism spectrum disorder, and congenital anomalies," appears online in The American Journal of Human Genetics April 12, 2018.

Related Stories

Discovery of X-linked intellectual disability syndrome is aided by web tools

December 3, 2015
It's a genetic detective story with a distinct 21st-century flavor. A geneticist from Cold Spring Harbor Laboratory (CSHL) in the United States has used powerful internet and social media tools to find doctors and researchers ...

Seven genes for X-linked intellectual disability

February 13, 2015
X-linked intellectual disability is a disorder that predominantly affects men and can have highly variable clinical manifestations. Scientists at the Max Planck Institute for Molecular Genetics in Berlin have found seven ...

Researchers find genetic cause of new type of muscular dystrophy

February 9, 2017
A newly discovered mutation in the INPP5K gene, which leads to short stature, muscle weakness, intellectual disability, and cataracts, suggests a new type of congenital muscular dystrophy. The research was published in the ...

Gene that causes intellectual disability when mutated finally identified

July 29, 2015
At least half of those with an intellectual disability across the world do not have a formal diagnosis. However, thanks to new DNA sequencing technology, along with the expertise and perseverance of University of Adelaide ...

Mutations common in pancreatic CA, history of other cancers

February 7, 2018
(HealthDay)—A substantial proportion of individuals with pancreatic cancer and a history of other hereditary breast and ovarian cancer (HBOC)- or Lynch syndrome (LS)-related cancers have mutations in a prostate cancer susceptibility ...

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 ...

Recommended for you

Variants in non-coding DNA contribute to inherited autism risk

April 19, 2018
In recent years, researchers have firmly established that gene mutations appearing for the first time, called de novo mutations, contribute to approximately one-third of cases of autism spectrum disorder (ASD). In a new study, ...

Researchers discover link between gene variation and language

April 18, 2018
What shapes the basic features of a language?

Natural selection still at work in humans

April 18, 2018
Evolution has shaped the human race, with University of Queensland researchers finding signatures of natural selection in the genome that influence traits associated with fertility and heart function.

Gene therapy for beta-thalassemia safe, effective in people

April 18, 2018
In a powerful example of bench-to-bedside science showing how observations made in the lab can spark life-altering therapies in clinic, an international team of clinician-investigators has announced that gene therapy for ...

Potential lines of attack against prostate cancer

April 17, 2018
Researchers from The University of East Anglia (UEA) have contributed to the world's largest study into genes that drive prostate cancer – identifying 80 molecular weaknesses that could be targeted by drugs to treat the ...

Epstein-Barr virus linked to seven serious diseases

April 16, 2018
A far-reaching study conducted by scientists at Cincinnati Children's reports that the Epstein-Barr virus (EBV)—best known for causing mononucleosis—also increases the risks for some people of developing seven other major ...

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.