Researchers at Redcliffe Labs have reported a previously undocumented variant in the TAPT1 gene in a fetus with nonimmune hydrops fetalis and skeletal abnormalities, a diagnosis that routine chromosomal testing could not reach.

The case report, published in the journal Clinical Dysmorphology, is titled “Nonimmune hydrops fetalis with skeletal dysplasia due to a novel homozygous recessive TAPT1 splice-donor variant.” It was co-authored by Dr Himani Pandey, Dr Varun Venket, Dr Shivani Mishra and Aayushi Gupta of Redcliffe Labs’ Department of Molecular Genetics, with researchers from collaborating institutions.

The case in view

A 22-year-old pregnant woman was referred for a detailed second-trimester ultrasound. The couple was not related by blood, and she had had an earlier first-trimester pregnancy loss. The scan showed generalised swelling beneath the fetal skin and fluid around the lungs, heart and abdomen. It also showed a small head circumference, short long bones with bowing of the femurs, bilateral talipes (feet turned inward and downward) and a Blake’s pouch cyst at the back of the brain.

The findings fit nonimmune hydrops fetalis (NIHF), defined by abnormal fluid build-up in at least two fetal body compartments. It can have several causes, including genetic disorders, and some cases stay unexplained after initial tests.

What the tests found

Chromosomal microarray analysis (CMA) at Redcliffe Labs found no definitive chromosomal abnormality: no trisomy, monosomy, polyploidy or copy-number variations. It did show long stretches of homozygosity, 31.14 Mb on chromosome 4 and 13.53 Mb on chromosome 10. These can appear even when parents are unrelated, for example through shared ancestry.

Because the microarray was not diagnostic, the laboratory ran whole-exome sequencing on the amniotic fluid sample. It identified a likely pathogenic homozygous splice-donor variant, TAPT1 c.1236+1G>A. According to the authors, it has not been reported in the ClinVar or gnomAD v4 databases. Sanger sequencing confirmed it in the fetal amniotic fluid and, as a heterozygous finding, in the mother. The father was unavailable for confirmation testing. Computer-based prediction suggested the variant would cause exon 11 to be skipped during RNA processing, producing a shortened TAPT1 protein.

The TAPT1 gene is involved in cellular processes relevant to skeletal development, and variants in it have been linked to osteochondrodysplasia, a group of disorders affecting bone and cartilage. The authors say only 17 cases had been reported in the literature at the time of publication and that, to their knowledge, theirs is only the second documented case of TAPT1-associated osteochondrodysplasia from India.

Why the authors say it matters

The researchers argue the case shows the value of combining prenatal imaging with genomic testing. Ultrasound can show structural abnormalities but not their cause, and microarray analysis can detect chromosomal changes but may miss certain sequence variants. In pregnancies with multiple abnormalities and inconclusive first results, exome sequencing can identify genetic causes and support genetic counselling and informed reproductive decisions.

The release cites a 2026 study from Western Rajasthan in which whole-exome sequencing found disease-associated variants in 36.6% of 41 fetuses with NIHF who were tested. The figure is specific to that group.

Dr Pandey said such testing “can support clearer diagnoses, strengthen genetic counselling and help families make informed decisions about future pregnancies.” Aditya Kandoi, founder and chief executive of Redcliffe Labs, said investments in advanced diagnostics and research “are essential to improve our understanding of these disorders and help clinicians identify their underlying causes.”

Limits to keep in mind

This is a single-case report, so it shows what testing found in one family, not how often such testing succeeds. The variant is classed as likely pathogenic, not confirmed pathogenic, and the splicing effect is predicted by software rather than shown in laboratory experiments. The father’s sample was not available. The release does not state the outcome of the pregnancy or what follow-up the family received.

Redcliffe Labs says its genomic services include chromosomal microarray analysis, whole-exome and clinical exome sequencing, targeted genetic testing and Sanger sequencing.