The doctors further studied the gene and found that its malfunction affects multiple tissues, resulting in a deadly condition, that they have named as "Lethal Serpinopathy."
Published Aug 25, 2024 | 7:00 AM ⚊ Updated Aug 25, 2024 | 11:55 AM
Foetal abnormality leads to discovering new disease in NIMS. (AI generated)
Over the period of time, Hyderabad-based institutions, the Department of Medical Genetics at Nizam’s Institute of Medical Sciences (NIMS) and the Centre for DNA Fingerprinting & Diagnostics (CDFD), observed a couple who was not able to conceive a child.
Despite not being related by blood, the couple faced many difficulties through the multiple pregnancies. Through two medical terminations of pregnancies and the loss of a newborn baby, the doctors observed one thing in common— fluid buildup around the chest and heart area.
Following this, the team of doctors from NIMS and CDFD conducted a series of advanced DNA sequencing tests on the terminated foetus leading to the discovery of a new disease caused due to a previously unknown mutation in the SERPINA11 gene.
How did the doctors discover the gene mutation and what are its effects?
The couple faced a heartbreaking situation during their 23rd week of pregnancy when an ultrasound revealed fluid buildup around the heart of their unborn baby.
However, it was not the first time the couple had faced such an issue, tragically, they had previously lost a newborn who suffered from a similar condition involving fluid in the chest.
Given this history and the recurrence of the issue, doctors performed genetic testing through amniocentesis— a prenatal procedure where a small sample of amniotic fluid from a pregnant woman’s uterus is removed to test for genetic or chromosomal conditions in the baby.
The couple then decided to terminate the pregnancy, and the foetus was examined after termination.
The examination revealed mild swelling under the skin and subtle facial differences, but no major external malformations. Inside the chest, there was a small amount of fluid around the heart, along with small cysts on the lungs. The organs in the abdomen appeared mostly normal, except for similar cysts on the liver and intestines.
“Bilateral pleural effusion and multiple similar cysts were noted on the lung surfaces, more in the dependent portions. Intrathoracic structures were structurally normal otherwise. Intra-abdominal structures were grossly normal but for similar thin-walled cystic lesions containing honey-coloured gelatinous fluid on the liver surface and along the intestines,” found the researchers while examining the foetus.
Throughout their ordeal, the couple conceived two more times. One of these pregnancies resulted in the birth of a healthy baby girl, but in the next pregnancy, fluid was again detected around the heart and lungs of the foetus during an ultrasound at 19 weeks.
This pregnancy was also terminated, and the findings in this foetus were similar to those seen in the earlier case. This led to the discovery of a mutation in the SERPINA11 gene, linked to a severe and deadly condition observed in two foetuses.
Dr Shagun Aggarwal, Head of the Department of Medical Genetics, and Dr Prajnya Ranganath, Additional Professor at NIMS, along with their team, conducted detailed tests on a second foetus (which was medically aborted) using advanced DNA sequencing.
It was during these tests that they discovered a mutation in the SERPINA11 gene, leading to the identification of a new disease, a world-first, said NIMS in a statement.
The CDFD team, led by Dr Rashna Bhandari and Dr Ashwin Dalal, further studied the gene and found that its malfunction affects multiple tissues, resulting in a deadly condition, that they have named as “Lethal Serpinopathy.”
This study, to be published in the September 2024 issue of the Clinical Genetics journal, reveals a new genetic disease in a family with recurring pregnancy issues.
Telangana Health Minister Damodar Rajanarasimha congratulated the Department of Medical Genetics, NIMS director Dr Birappa and the laboratory staff for conducting excellent research on genetic disorders and achieving a rare clinical achievement in the world.
The minister said that the reputation of NIMS Hospital and Telangana State Medical and Health Department will be recognized at the international level due to this research.
రాష్ట్ర వైద్య ఆరోగ్య కుటుంబ సంక్షేమ శాఖ మంత్రి దామోదర్ రాజనర్సింహ గారిని హైదరాబాద్లోని తెలంగాణ రాష్ట్ర సచివాలయంలో ప్రపంచ బ్యాంకు ప్రతినిధులు సమావేశమయ్యారు.
ఈ సమావేశంలో తెలంగాణ రాష్ట్ర ప్రభుత్వం వైద్య, ఆరోగ్య, కుటుంబ సంక్షేమానికి ప్రోత్సాహం అందించడానికి చేస్తున్న కృషిని ప్రపంచ… pic.twitter.com/cl4a1VWhdQ
— Damodar Raja Narasimha (@DamodarCilarapu) August 23, 2024
The researchers said that the SERPINA11 gene is active in both humans and mice, even though it’s not very common in large amounts in any specific tissue. Based on its similarities to other genes, SERPINA11 likely works by blocking certain proteins.
The damage seen in the internal connective tissues and membranes of affected fetuses suggests that the SERPINA11 gene helps maintain the stability of these tissues by blocking certain enzymes called serine proteases.
“Generalised extracellular matrix disruption in internal visceral connective tissue and membranes in affected foetuses reported here suggests SERPINA11 involvement in extracellular matrix homeostasis by inhibition of tissue serine proteases,” said the researchers.
The specific genetic mutation, confirmed by advanced lab techniques, along with tests on fetal lung tissue, suggests that the deadly condition seen around birth is due to the absence of the SERPINA11 protein.
The researchers found that this gene is really important for keeping connective tissues healthy because it stops certain enzymes from causing problems.
If this protein isn’t there, it can lead to serious issues during the development of a foetus. Another study found a change in this gene in a foetus with a condition called hydrops, but that still needs more research to understand exactly how SERPINA11 works. This includes figuring out its structure, what proteins it affects, and whether it works inside cells or is released outside them.
“This gene seems to play a crucial role in maintaining the balance of connective tissues by blocking certain enzymes. When this protein is missing, it leads to life-threatening problems during fetal development. Although another study found a variation of this gene in a fetus with a condition called hydrops, more research is needed to fully understand how SERPINA11 works, including its structure, the proteins it targets, and whether it functions inside cells or is secreted outside them,” said the researchers.
(Edited by Sumavarsha Kandula.)
