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A research paper by Redcliffe Labs researchers and other collaborating institutions, published in Clinical Dysmorphology, reports the identification of a novel TAPT1 gene variant in a fetus with nonimmune hydrops fetalis (NIHF) and skeletal abnormalities. The findings highlight how advanced genomic testing can help establish the genetic basis of rare fetal disorders when conventional investigations do not provide a definitive diagnosis.



Titled “Nonimmune hydrops fetalis with skeletal dysplasia due to a novel homozygous recessive TAPT1 splice-donor variant,” the study examines a prenatal case involving multiple fetal abnormalities that required further genetic evaluation. The research was co-authored by Dr. Himani Pandey, Dr. Varun Venket, Dr. Shivani Mishra, and Miss. Aayushi Gupta from Redcliffe Labs’ Department of Molecular Genetics, along with other researchers.



The case involved a 22-year-old pregnant woman referred for a detailed second-trimester ultrasound. The couple was non-consanguineous, and the woman had experienced a previous first-trimester pregnancy loss. The scan revealed generalised swelling beneath the fetal skin, fluid accumulation around the lungs and heart, and fluid in the abdominal cavity. Other findings included a small head circumference, short long bones with bowing of the femurs, bilateral talipes, a condition in which the feet turn inward and downward, and a Blake’s pouch cyst in the posterior region of the brain.



These findings were consistent with NIHF, a condition characterised by abnormal fluid accumulation in at least two fetal body compartments. Although NIHF can have several underlying causes, including genetic disorders, some cases remain unexplained after initial investigations.



India’s growing focus on genomic research is helping improve our understanding of genetic disorders. A 2026 study from Western Rajasthan found that whole-exome sequencing identified disease-associated genetic variants in 36.6% of the 41 fetuses with nonimmune hydrops fetalis who underwent testing. While the findings are specific to the study group, they highlight how advanced genetic testing can help identify the causes of complex fetal abnormalities.



Chromosomal microarray analysis (CMA), performed at Redcliffe Labs, did not identify a definitive chromosomal abnormality. However, it revealed long contiguous stretches of homozygosity (LCSH), measuring 31.14 Mb on chromosome 4 and 13.53 Mb on chromosome 10. No trisomy, monosomy, polyploidy, or copy-number variations were detected. LCSH can occur even when parents are not related, for example through shared ancestry.



As the CMA was non-diagnostic, whole-exome sequencing (WES) of the amniotic fluid sample was also performed at Redcliffe Labs. It identified a likely pathogenic homozygous splice-donor variant in the TAPT1 gene, written as TAPT1 c.1236+1G>A, which, to the authors’ knowledge, has not been reported in the ClinVar or gnomAD v4 databases. The variant was confirmed through Sanger sequencing in the maternal sample (heterozygous) and fetal amniotic fluid. The father was unavailable for confirmation testing. Computational (in silico) analysis predicted that the likely pathogenic variant would cause exon 11 to be skipped during RNA processing, resulting in a truncated TAPT1 protein.



According to the researchers, only 17 cases had been reported in the literature at the time of publication. To the authors’ knowledge, this study represents only the second documented case of TAPT1-associated osteochondrodysplasia from India, expanding the known range of genetic variants associated with the condition.



The TAPT1 gene is involved in cellular processes relevant to skeletal development. Disease-associated variants in this gene have been linked to osteochondrodysplasia, a group of disorders affecting bone and cartilage development. In this case, the identified likely pathogenic variant offered a potential molecular explanation for the fetal abnormalities.



The case highlights the value of combining prenatal imaging with advanced genetic testing. While ultrasound can identify structural abnormalities, it may not establish their genetic cause. CMA can detect chromosomal changes but may not identify certain sequence variants. In cases involving multiple fetal abnormalities and inconclusive initial findings, WES can help uncover genetic causes and support genetic counselling and informed reproductive decision-making.



Dr. Himani Pandey, Lab Head – Genomics, Redcliffe Labs, and co-author of the study, said: “This case highlights how advanced genomic testing can help identify the underlying cause of rare fetal disorders. By detecting genetic variants that may not be identified through conventional investigations, such testing can support clearer diagnoses, strengthen genetic counselling and help families make informed decisions about future pregnancies.”



Aditya Kandoi, Founder & CEO, Redcliffe Labs, commented: “Every rare genetic condition presents families with questions that can be difficult to answer. Investments in advanced diagnostic capabilities and research are essential to improve our understanding of these disorders and help clinicians identify their underlying causes. By documenting clinical findings and contributing to scientific knowledge, we aim to support more informed diagnosis and clinical decision-making. Our continued investment in accessible, advanced diagnostics reflects our commitment to helping families across India find answers and make informed decisions about their healthcare.”



The laboratory’s genomic capabilities include chromosomal microarray analysis, whole-exome sequencing, clinical exome sequencing, targeted genetic testing, and Sanger sequencing, supporting the investigation of rare inherited disorders and complex clinical presentations.



The publication reflects Redcliffe Labs’ continued contribution to clinical research on rare genetic conditions. By documenting novel variants and their clinical significance, the study adds to scientific understanding of TAPT1-related disorders.