KMC doctors discover new gene causing human limb abnormalities

The Department of Medical Genetics at Kasturba Medical College, Manipal, collaborated with Institute of Medical Biology, A*STAR, Singapore and Istanbul University, Turkey, to discover a new gene as a cause of human limb abnormalities or tetra amelia syndrome.

The Manipal team led by Dr Girish Katta, comprising Dr Anju Shukla and Dr Shalini S Nayak, along with the international teams found that mutations in R-spondin 2 (RSPO2) gene as the cause of the condition.

“These doctors offer postnatal evaluation of fetuses as a routine clinical service. They came across a consanguineous family (parents who are close relatives) with three consecutive pregnancies affected by complete or partial absence of all four limbs, along with agenesis of lungs and cleft lip and palate,” said Dr Pragna Rao Dean KMC, Manipal, while giving the details of the discovery.

“The international collaboration then brought together more affected families and discovered the mechanism of disease,” she added.

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 highly reputed journal ‘Nature’ published by Nature Publishing Group.

Dr Girish 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 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.”

Dr Girish added that the Department of Science and Technology, New Delhi, partially funded the work.

Dr H Vinod Bhat, Vice Chancellor of Manipal Academy of Higher Education (MAHE) appreciated the hard work done by the Department of Medical Genetics in identifying the genetic causes of human diseases.

He 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).

“The MAHE is working towards becoming one of the best research centres globally,” said Dr Bhat.

Dr Poornima Baliga, Pro Vice Chancellor (Health Sciences) and Dr N Udupa, Prof and Research Director (Health Sciences) congratulated the team for the discovery.