Department of Medical Genetics, Kasturba Medical College, Manipal partner

The collaboration aims to discover a new gene as a cause of human limb abnormalities and /or tetra amelia syndrome

Department of Medical Genetics at Kasturba Medical College, Manipal has collaborated with Institute of Medical Biology, A*STAR, Singapore and Istanbul University, Turkey for discovering a new gene as a cause of human limb abnormalities and /or tetra amelia syndrome. Eleven affected individuals from five families from the different parts of the world were noted to have either complete absence or deficiency of upper and lower limbs along with small or absent lungs and cleft lip and cleft palate. The work has been now published in a journal Nature.

The Manipal team led by Dr Girish Katta comprising Dr Anju Shukla and Dr Shalini S Nayak collaborated with international teams for the discovery of mutations in RSPO2 gene as the cause of the condition. The team offers postnatal evaluation of fetuses as a routine clinical service and came across a consanguineous family with three consecutive pregnancies affected with complete or partial absence of all four limbs along with agenesis of lungs and cleft lip and palate, Dr Pragna Rao said, giving the details of the discovery. The international collaboration then brought together more affected families and discovered the mechanism of disease, she noted.

Dr Katta said, the study not only identified the cause of human limb abnormalities or tetra amelia syndrome but also explains the mechanism of how exactly the defect in RSPO2 (R-spondin 2) gene leads to deficiencies in limb and lung growth by conducting several experiments on HEK293T and HEK293T-STF cell lines and animal models such as mouse and frog. He added, the paper discovered that RSPO2 signaling is LGR-independent (receptor for the R-spondin secreted ligands) for the limb, lung and vascular development. Dr Girish also acknowledged the Department of Science and Technology, New Delhi, India for partially funding this work.

Talking to the media on the discovery Dr H Vinod Bhat, Vice Chancellor, Manipal Academy of Higher Education appreciated the hard work done by the Department of Medical Genetics in identifying the genetic causes of human diseases. Dr Bhat also added that a new neurodevelopmental disorder ‘Multiple mitochondrial dysfunction syndrome’ and a bone disease ‘Short rib thoracic dysplasia type 16’ were also identified by this team and these are already catalogued in Online Mendelian Inheritance in Man (OMIM).

Dr N Udupa, Directorate of Research and Dr Poornima Baliga, Pro Vice Chancellor of Manipal Academy of Higher Education were present during the occasion.