New Delhi: The study identifies a novel TAPT1 gene variant associated with nonimmune hydrops fetalis and skeletal dysplasia, expanding scientific understanding of a rare inherited disorder.
Redcliffe Labs researchers, along with collaborators from other institutions, have identified a novel TAPT1 gene variant associated with nonimmune hydrops fetalis (NIHF) and skeletal abnormalities in a fetus.
The research, published in the journal Clinical Dysmorphology, highlights how advanced genomic testing can help establish the genetic basis of rare fetal disorders when conventional investigations fail to 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 researchers from other collaborating institutions.
TAPT1 Study Examines Rare Fetal Abnormalities
The case involved a 22-year-old pregnant woman who was referred for a detailed second-trimester ultrasound. The couple was non-consanguineous, and the woman had experienced a previous first-trimester pregnancy loss.
The ultrasound revealed generalised swelling beneath the fetal skin, fluid accumulation around the lungs and heart, and fluid in the abdominal cavity.
Other abnormalities 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 nonimmune hydrops fetalis (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 even after initial investigations.
The identification of a potentially disease-causing TAPT1 variant in this case provides a possible molecular explanation for the observed fetal abnormalities.
Advanced Genetic Testing Identifies TAPT1 Variant
As part of the investigation, chromosomal microarray analysis (CMA) was performed at Redcliffe Labs.
The test did not identify a definitive chromosomal abnormality but 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.
Since the chromosomal microarray analysis was non-diagnostic, researchers proceeded with whole-exome sequencing (WES) of the amniotic fluid sample at Redcliffe Labs.
The WES analysis identified a likely pathogenic homozygous splice-donor variant in the TAPT1 gene, designated as TAPT1 c.1236+1G>A.
According to the researchers, to their knowledge, this variant had not previously been reported in the ClinVar or gnomAD v4 databases.
The variant was confirmed through Sanger sequencing in the maternal sample, where it was found in a heterozygous state, and in the fetal amniotic fluid sample. The father was unavailable for confirmation testing.
Computational (in silico) analysis predicted that the likely pathogenic TAPT1 variant would cause exon 11 to be skipped during RNA processing, resulting in a truncated TAPT1 protein.
TAPT1-Related Disorder: Limited Cases Reported Worldwide
According to the researchers, only 17 cases of the condition had been reported in scientific literature at the time of publication.
To the authors’ knowledge, the study represents only the second documented case of TAPT1-associated osteochondrodysplasia from India. The findings expand the known range of genetic variants associated with this rare 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 that affect bone and cartilage development.
In the reported case, the identified likely pathogenic TAPT1 variant offered a potential molecular explanation for the combination of nonimmune hydrops fetalis and skeletal abnormalities observed during prenatal evaluation.
Advanced Prenatal Genomic Testing Helps Identify Genetic Disorders
The research also highlights the importance of advanced genomic testing in investigating unexplained fetal abnormalities.
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 these findings are specific to the study group, they demonstrate how advanced genetic testing can help identify the underlying causes of complex fetal abnormalities.
In the reported TAPT1 case, the combination of prenatal imaging and genetic investigations helped researchers move beyond the initial identification of structural abnormalities towards a possible molecular diagnosis.
Ultrasound can identify structural abnormalities in a fetus but may not establish their genetic cause. Similarly, chromosomal microarray analysis can detect chromosomal changes but may not identify certain sequence variants.
Whole-exome sequencing can help identify genetic causes in cases involving multiple fetal abnormalities when conventional investigations do not provide a definitive diagnosis.
Such findings can also support genetic counselling and informed reproductive decision-making.
Redcliffe Labs Highlights Role of Genomic Diagnostics
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.”
Redcliffe Labs’ Genomic Testing Capabilities
Redcliffe Labs‘ genomic capabilities include chromosomal microarray analysis, whole-exome sequencing, clinical exome sequencing, targeted genetic testing, and Sanger sequencing.
These diagnostic capabilities support 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 the scientific understanding of TAPT1-related disorders and highlights the role of advanced genomic testing in identifying the genetic causes of unexplained fetal abnormalities.
