Mar 29, 2019 New overgrowth gene identified

A new overgrowth syndrome has been identified after finding a mutation that affects bone development

Scoliosis, or twisting of the spine, is a common characteristic of an overgrowth syndrome

Reproduced with permission from reference 1 © 2018 Elsevier

Genetic analyses in two adolescent girls with similar features has led to the identification of a novel overgrowth syndrome.

The research, conducted by a team of scientists at Keio University School of Medicine and published in 2015, pinpointed a specific amino acid substitution in a gene called platelet-derived growth factor receptor B (PDGFRB) as being causative of the syndrome1. The research also suggested that the antileukaemic drug imatinib mesylate, which targets this gene, could have a therapeutic benefit.

Research conducted by another team in Belgium, published just over a year later in 2016, confirmed that patients with the mutation are sensitive to the drug

“Overgrowth syndromes are caused by aberrations in various signaling pathways,” explains Kenjiro Kosaki of the University's Center for Medical Genetics. “We showed that abnormal PDGFRB signaling leads to overgrowth associated with multi-organ defects.”

The team identified two adolescent girls in Japan with similar overgrowth features but who did not have mutations in the genes that are normally associated with known overgrowth syndromes. Both girls were tall, with long limbs and extremities. They also had distinctive facial features, hyperelastic and fragile skin, scoliosis, white matter lesions in the brain, and neurological symptoms that started in childhood and adolescence.

Genetic analyses found a specific amino acid substitution in the PDGFRB gene that was present in both girls but not in their parents. Prediction programs suggested that this particular amino acid substitution was highly likely to have functional effects.

PDGFRB plays a critical role in cell growth and differentiation. PDGFRB mutations have been reported in people with idiopathic basal ganglia calcification: this means they have abnormal calcium deposits in a part of the brain, leading to neuropsychiatric manifestations.

The white matter lesions in the brains of the two girls in this study could represent an early stage of this disease.

PDGFRB mutations have also been found in people with a disease called infantile myofibroma, a rare, benign soft tissue tumour that develops in children. One of the two Japanese girls had developed on her jaw a myofibroma that was removed at the age of eight.

The team suggested that the amino acid substitution in the two girls exerts a specific effect on bone formation, resulting in their unique clinical presentation.

The research findings should prompt the recognition of a novel overgrowth syndrome caused by mutation of the gene, the researchers concluded.

The program-affiliated researchers contributing to this research are from Center for Medical Genetics, Keio University School of Medicine, Japan.


  1. Takenouchi, T., Yamaguchi, Y., Tanikawa, A., Kosaki, R., Okano, H., & Kosaki, K. Novel overgrowth syndrome phenotype due to recurrent de novo PDGFRB mutation. The Journal of Pediatrics 166, 483–486 (2015). | Article
  2. Arts, F. A., Chand, D., Pecquet, C., Velghe, A. I., Constantinescu S., et al. PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib. Oncogene 35, 3239–3248 (2016). | Article

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