Mumbai scientists identify six genes behind foetal defects

Over three years, 44 44 medically terminated foetuses with abnormalities were examined to study recurring factors

MUMBAI: Scientists in Mumbai have identified six new genes associated with severe foetal abnormalities, including brain deformities and congenital heart defects, which could help parents make informed decisions while raising children with these conditions.

Mumbai scientists identify six genes behind foetal defects

The discovery was made by scientists at the Indian Council of Medical Research – National Institute for Research in Reproductive Health (ICMR-NIRRCH), in collaboration with the Nowrosjee Wadia Maternity Hospital in Parel.

The findings, published in the Indian Journal of Medical Research in June, and available since August, are based on a three-year study conducted until 2024. The research team examined 44 medically terminated foetuses after ultrasound scans revealed abnormalities.

Standard genetic testing confirmed known chromosomal conditions such as trisomy 21 (Down’s Syndrome) and trisomy 13 (Patau Syndrome) in four cases. But researchers said that many abnormalities often remain unexplained after such routine tests. To investigate further, they used whole-exome sequencing (WES), which scans thousands of genes in foetal tissue and has recently emerged as a powerful tool for uncovering single-gene causes of developmental disorders.

Through WES, six new genes known as “candidate genes” were identified – RUNX2, PALLD, KMT2D, FBN2, CPLANE1 and KDM1A – all of them associated with brain anomalies such as spinal dysraphism, holoprosencephaly, Dandy-Walker malformation, and congenital heart disease. Importantly, the PALLD gene was linked to neural tube or brain defects in humans for the first time.

The research was conducted by a four-member team led by Dr Shailesh Pande, medical geneticist, head of department, Genetic Research Centre (GRC), ICMR-NIRRCH. Other GRC scientists include Dr DVS Sudhakar and Dr Shaini Joseph, and Dr Vandana Bansal, professor of obstetrics and gynaecology and foetal medicine expert from Nowrosjee Wadia Maternity Hospital.

“Foetal malformations affect nearly 5% of pregnancies worldwide and are among the leading causes of pregnancy loss, stillbirths and infant morbidity. Conventional tests can detect chromosomal abnormalities, but more than half of such cases remain unexplained,” said Dr Pande.

He added that the six newly associated genes shed light on conditions that otherwise may go undiagnosed. “Such pregnancies are often terminated naturally because the foetus is unable to survive. Even if gestation continues, it can result in more severe abnormalities,” he said.

Researchers emphasised that early detection can ease the psychological and financial burden faced by families. Pande said, “Since 95% of genetic conditions currently have no cure, prevention and timely identification become crucial.”

He also noted the importance of testing foetal tissue directly rather than relying solely on parental blood work, which may miss certain mutations.

The study, doctors said, has implications not just for diagnosis but also for counselling. Identifying genetic causes can help clinicians assess recurrence risks and prepare couples for future pregnancies.

“Often parents discover such abnormalities very late, or even after birth, which adds to the trauma. Detecting them at the right stage allows families to make informed decisions much earlier,” Dr Pande said.

Dr Bansal added that abnormalities could arise from genetic mutations, environmental triggers, or maternal health factors such as diabetes and obesity. “Early testing will help us guide parents better. Counselling and treatment based on the specific cause can also help prevent recurrence in some cases,” she said.

The researchers stressed that such findings carry wider public health value. “In India, most families rely on public hospitals for antenatal care. Demonstrating that advanced genetic tools such as WES can be used in these settings shows that genomics is no longer limited to private labs or research centres. These six novel candidate genes now give us critical insights into why some abnormalities occur,” said Dr Pande, adding that further studies with animal models will confirm the role of the genes in the deformities.