New study links SOX17 mutations to severe PAH in children, some adults
Genetic differences may help explain when disease first appears
Written by |
Mutations in the gene SOX17 are linked to a severe form of pulmonary arterial hypertension (PAH) that most often manifests in childhood, though these mutations are also found in some adults with adult-onset PAH, according to a new study.
Findings suggest that the specific type and location of mutations in the SOX17 gene may influence the age of PAH onset. More research is needed to fully understand how SOX17 mutations contribute to the disease, but researchers said the findings highlight the importance of genetic testing.
The study, “SOX17 variants are associated with severe pulmonary arterial hypertension with and without congenital heart disease,” was published in the International Journal of Cardiology.
PAH is marked by abnormally high pressure in the blood vessels that carry blood from the heart to the lungs, which puts extra strain on the heart. While many cases of PAH are idiopathic, meaning the cause is unknown, some forms are linked to genetic mutations. Mutations in the SOX17 gene are a rare genetic cause of PAH, but researchers are still working to understand how the disease develops and progresses in people with these mutations.
Children with SOX17 mutations often had severe disease
In this study, researchers in the U.K. reported outcomes from eight children with PAH who had SOX17 mutations. Most also had congenital heart disease, and many had severe illness. Common symptoms at diagnosis included blue skin, lips, and/or nails — a sign of low oxygen levels — and shortness of breath.
Two children required lung transplants, and a third died while waiting for a transplant. Two others underwent a surgical procedure called a Potts shunt, which is designed to help reduce pressure on the right side of the heart. Both of those children died up to nine months after the surgery.
“Despite aggressive [treatment], clinical response and outcomes were poor in this cohort of patients,” the researchers wrote.
In addition to these eight patients, the researchers also reviewed previously published reports describing dozens of other cases of SOX17-related PAH.
They found that about two-thirds of people with SOX17 mutations were diagnosed with PAH during childhood, with a median age at diagnosis of about 5 years. In the remaining cases, diagnosis occurred in adulthood, with a median age of 33 years. People without congenital heart disease tended to be diagnosed at older ages than those who had heart defects.
Mutation location may influence age when PAH develops
The researchers also found that mutation location may help explain differences in the timing of disease onset. More than half of patients with childhood-onset PAH had mutations in a specific region of the SOX17 gene called the HMG-box domain. By contrast, only about 1 in 5 patients with adult-onset PAH had mutations in this region.
“Rare and deleterious SOX17 variants have been reported more frequently in children compared to adults with increased occurrence of variants in the HMG-box domain in childhood-onset PAH,” the researchers concluded.
The researchers wrote that more studies are needed to understand how mutations in different regions of SOX17 contribute to disease. They also emphasized the importance of expanding genetic testing so children with SOX17 mutations can be diagnosed earlier and receive appropriate care.
