German researchers at the University Medical Centre Hamburg-Eppendorf made a ground-breaking finding by identifying a mutation in the TMCO3 gene in twins using next-generation sequencing, shedding light on the underlying genetic basis of a rare and previously unknown disorder.

TMCO3, short for trans-membrane and coiled-coil domain-containing protein 3, is a gene responsible for coding a protein involved in various cellular processes.

The mutaion in the TMCO3 gene has been linked to a range of symptoms observed in the affected twins, including developmental delays, intellectual disabilities, and distinctive physical features.

This breakthrough not only provides valuable insights into the understanding of human genetics but also opens the doors to potential therapeutic interventions and improved genetic counselling for affected individuals and their families.

The utilisation of next-generation sequencing in this research has not only facilitated the identification of this specific mutation but has also paved the way for further exploration into the intricate world of genomics and its implications for human health.

The findings of the research published in the Journal of Bone and Mineral Research recently revealed that the TMCO3 protein is expressed by chondrocytes, cells responsible for bone growth and that it regulates the expression of two other proteins known to control bone growth (parathyroid hormone-related protein and Indian hedgehog).

TMCO3 appears to transport protons in exchange for potassium across a protein-packaging organelle within cells.

The scientists confirmed that the mutation in TMCO3 was responsible for the short stature of the sisters by analysing a mouse model lacking the gene and showing that the mice had shortened bones.

"This paper is the result of a great collaboration between the Institute of Human Genetics and the Department of Osteology and Biomechanics, both located at the University Medical Centre Hamburg-Eppendorf, in Germany. It shows the importance of ion and pH homeostasis in organismal growth," said corresponding author Dr Kerstin Kutsche said.