A recent study published in Genetics in Medicine has identified the gene GPKOW as being associated with a multisystemic X-linked developmental disorder. The research, conducted by Baylor College of Medicine, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, and other institutions, found rare variants in the GPKOW gene on the X-chromosome to be the cause of severe symptoms such as restricted fetal growth, microcephaly, and significant brain and eye abnormalities.
Researchers utilized whole-exome sequencing to analyze patients and their parents, discovering variants in GPKOW, a gene vital to mRNA processing. Functional studies using Drosophila, or fruit fly models, by Baylor's Center for Precision Medicine Models helped establish these variants as disease-causing. "We found that the fly ortholog of GPKOW is critically important to survival in the fly," stated Dr. Jung-Wan Mok from Baylor.
The study noted that the GPKOW variant acts as a partial loss-of-function allele. This presents severe symptoms in males who have only one copy of the gene, whereas females, with one normal gene copy, display milder symptoms like short stature and vision issues. Dr. Keren Machol of Baylor highlighted the potential impact of these findings on clinical management and further research. Dr. Shinya Yamamoto added that documenting GPKOW as a disease-causing gene will assist in identifying affected individuals and advancing research.
This collaborative effort included contributions from researchers such as Laura Mackay, Maria Blazo, and many others. The work received support from several research bodies, including the National Institutes of Health, the Korean Ministry of Education, and the National Health and Medical Research Council.
