Credit: CDC
Key Points:
- Researchers have zeroed in on two specific genes linked to neurodevelopmental deficits, including microcephaly in children.
- The findings were validated in a zebrafish model.
- The research will add two genes to diagnostic gene panel tests for children going forward.
The Zika outbreak of 2016 in Brazil, where the Summer Olympics were scheduled to be held, led to an unprecedented amount of mainstream coverage of the ever-present disease. This coverage included the symptom of microcephaly, a condition in which a baby is born with an abnormally small head.
In addition to its link to Zika infection in pregnant woman, microcephaly is a common manifestation of several different neurodevelopmental disorders. Now, Northwestern Medicine scientists have identified disease-causing DNA variants in two genes linked to microcephaly in children.
According to the study published in Nature Communications, compared whole exome sequencing data from 11 individuals with microcephaly, short stature, cardiac abnormalities and anemia. They found that DNA variants in two genes, SLF2 and SMC5, compromise protein stability and reduce the ability of cells to repair damaged DNA.
The team then tested the findings in an animal model by inactivating the SLF2 and SMC5 orthologs in the zebrafish genome.
“We measured the head size of the zebrafish and found that there was a significant reduction compared to normal siblings,” said Erica Davis, associate professor of pediatrics and cell and developmental biology and co-senior author of the study. “We also evaluated the patterning of the zebrafish’s face by measuring the cartilage structures and saw something similar to what was in this group of children.”
The research team says the findings will aid in the early detection and diagnosis of microcephaly and other conditions.
“The findings from this research will add two genes to diagnostic gene panel tests or clinical whole exome or genome sequencing tests that are being ordered for kids who present with microcephaly or a concern for neurodevelopmental disease,” said Davis.
Further research by the team will focus on better understanding the genes’ role in maintaining genome stability, and why the brain is so susceptible to disorders caused by disruptions in DNA replication, repair or cell division.
Information provided by Northwestern Medicine.